Editorial Cover Story ESOP/NZW 2011 Congress Report Oncology ...

Editorial 

Hope is a good breakfast but a bad supper 5 

ECOP www.esop.eu 

European Conference of 

Oncology Pharmacy 

Cover Story 

ESOP/NZW 2011 Congress Report 

Preparation of monoclonal antibodies: practice across 6 

Europe 

The role of a pharmacist according to patients 10 

Companion diagnostics and personalised cancer medicine 12 

An assessment of the pharmacist’s role in oncology trial 14 

management 

Breast cancer irradiation: 2011 update 16 

Extravasation of cytotoxics: there is still room for 18 

improvement 

Oncology Pharmacy Practice 

DNA repair in cancer therapy: beneficial or harmful 21 

Cold water reconstitution of Vidaza® with subsequent 24 

refrigerated storage prolongs drug stability 

A practical approach to oral tumour therapy 26 

Setting up a pharmacist-led chemotherapy clinic: a 28 

practical guide 

Update 

Clinical evaluation of lenograstim use in the Bank of 31 

Cyprus Oncology Centre 

Special Report 

Hospital workers perceptions about nanotechnology 35 

Announcement 34 

EJOP is published quarterly and mailed to more than 5,000 European oncology pharmacists, pharmacy 

technicians and subscribers in 33 countries; and distributed at major international and national conferences. 

EJOP is available online (www.ejop.eu). 

Guest Authors: 

Dr Mirjam Crul, Dr Ann-Sophie Franki, Dr Kathleen Simons,Anita Waldmann, Dr Jan Trøst Jørgensen, Maria 

Hersom, Dr Mikael Daouphars, Ewelina Korczowska, Dr Martin Sevec, Professor Dr Wolfgang Wagner, 

Dr Ursula Pluschnig, Shahla Farokhnia, Gunar Stemer, Professor Robert M Mader, Professor Dorothee C 

Dartsch, Dr Anthony Tutino, Dr Mei Lai, Jürgen Barth, Carl Booth,Andri Kouroufexi, Stavroula Theophanous- 

Kitiri, George Polykarpou, Dr Yiola Markou, Dr Evangelia Papadimitriou, Dr Nagwa Ibrahim, Dr Ali Al Zahrani, 

Dr Ashraf Al Alwan 

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The discussion about the future 

role of pharmacy is ongoing and 

at the European level several proposals 

from ministries or the 

pharmaceutical inspection have 

been tendered along the way to describe the 

possible needs. We know that several lobbying 

groups are working in Strasbourg, France, 

as well as in Brussels, Belgium, to bring about 

different points of view about the position of 

pharmacists. 

Unnoticed by the public, the path is being 

smoothed to ignore the resolution adopted by the 

Council of Europe Committee of Ministers in 

1997 [1]: 

- Recalling that the pharmacist’s evolving role is to ensure the 

safe and effective use of medicines by patients at the lowest cost, 

thus contributing to the welfare of the patients and the improvement 

of public health; 

- Considering the present trend to shift the focus of attention away 

from the preparation of medicines towards ensuring that they 

are appropriately prescribed and dispensed by pharmacists and 

correctly used by patients; 

- Considering that this trend requires legislative reform and 

changes in initial training, and makes ethical demands on the 

profession; 

- Considering that, in a changing economic and social environment, 

pharmacists must adapt and must bring up to date their 

knowledge, training and practice in order to play their full part 

in society; 

- Considering that the patient’s well-being must be at the centre of 

all pharmaceutical activity, that the pharmacist’s traditional 

focus on the medicine must be shifted to the patient, and that the 

pharmacist should become a provider of health care in which the 

patient occupies the central place … 

The understanding of the role of pharmacists is and was clear. 

Near to patients in collaboration with doctors, defining the multiprofessional 

work and improving their knowledge and expertise. 

Since that time the ESOP has developed four new editions of 

Quality Standard for the Oncology Pharmacy Service (QuapoS), 

whilst keeping in close contact with the European Commissioner 

for Health and Consumer Policy. The goal is to unify national 

conditions for preparing cytotoxics and to educate healthcare 

workers as well as patients. This was no preterm birth that could 

not be followed by pharmacists Europe-wide. It is an open guide- 

Editorial 

For personal use only. Not to be reproduced without permission of the publisher (copyright@ppme.eu). 

Hope is a good breakfast but a bad supper * 

Klaus Meier 

Editor-in-Chief 

line with an option for each country to 

enshrine it in national legislation. 

ESOP’s understanding has grown that we 

have to foster collaboration with the European 

CanCer Organisation (ECCO) because a joint 

platform insures a multi-professional 

approach and the opportunity to be recognised 

as full partners of healthcare teams. Apharmacist 

will again be present on the board of 

directors in the next legislative period. 

EJOP has now been published for five years 

and it plays its part in harmonising and 

encouraging the process of oncology pharmacy 

in Europe at the same time. 

Again, in this issue we are presenting the efforts of national work 

in the report about the preparation of monoclonal antibodies as well 

as the general role of pharmacists in oncology trial management. 

We get surprising views about the conditions for pharmacists 

from some countries. We can learn how in the UK the chemotherapy 

clinics can be led by pharmacists and follow the discussion 

from Saudi Arabia about hospital workers’ understanding of nanotechnology. 

Often work at the national level triggers a European 

discussion. So, a questionnaire will be sent to all our 2,600 

members about their understanding of nanotechnology in order to 

sensitise them to both the benefits and the risks. 

As history has taught us that the revolution devours its children, 

we are aware we must show our responsibility every day in our 

daily work in each country. We are proud to celebrate in January 

2012 the 20th NZW—clinical conference for oncology pharmacy 

departments—with nearly 1,000 participants and are sure that 

the first European Conference of Oncology Pharmacy in 

Budapest, Hungary in September 2012 will give all European 

oncology pharmacists a place of exchange and mutual support. 

We are able and willing to work the whole day in not only the 

hope but also in the solid conviction that pharmacists, as we 

understand ourselves, are needed and welcome. 

I am pleased and proud to be a president of such committed and 

convinced membership. 

*Sir Francis Bacon 

Reference 

1. Council of Europe Committee of Ministers [homepage on the Internet]. 

Resolution AP (97) 2 on the development of the function of pharmacists 

and the adaptation of their initial training. [cited 2011 Dec 15]. Available 

from: wcd.coe.int/ViewDoc.jsp?id=596013&Site=CM 

European Journal of Oncology Pharmacy • Volume 5 • 2011 • Issues 3-4 www.ejop.eu 

5

Cover Story - ESOP/NZW 2011 Congress Report 


Preparation of monoclonal antibodies: practice 

across Europe 

To ensure proper handling of monoclonal antibodies (mAbs), the hospital pharmacist has to consider the safety of 

the product, the safety of the patient, and the safety of the personnel compounding the drugs. We conducted a survey 

across Europe to investigate current practice. 

Introduction 

Ever since the first monoclonal 

antibodies (mAbs) became available, 

hospital pharmacists have 

been faced with the challenge of 

preparing them so that patients 

receive the correct dose, infusions 

are sterile, and pharmacy 

staff are protected from potentially 

harmful exposure. Formal 

studies investigating the risk of 

mAb-related occupational expo- 

Mirjam Crul 

PharmD, PhD 

sure have not yet been performed. Hence, when compounding 

parenteral formulations of these drugs in the hospital setting, 

the responsible pharmacist must subjectively assess the magnitude 

of risk. This raises several issues. Firstly, given that a 

large proportion of mAbs are administered to immunologically 

challenged patients, and sometimes with concomitant 

chemotherapy, a thorough aseptic technique which minimises 

the risk of microbiological contamination is pivotal. 

Secondly, most mAbs are dosed using body weight or body 

surface area. Therefore, a safe and validated method of calculating 

the correct amount of infusion concentrate to add to the 

diluent is required. 

Thirdly, occupational exposure of pharmacy and nursing personnel 

should be considered. Although most mAbs do not have a direct 

effect on DNA and are therefore not mutagenic or genotoxic, therapeutic 

exposure to some mAbs, e.g. muromonab, has been linked 

to tumour development [1], possibly via indirect pathways. Given 

that most hospital staff are only exposed to trace amounts of mAbs, 

this risk is likely to be very small. However, because evidence 

exists to show that rituximab, trastuzumab, and antiangiogenic 

mAbs such as bevacizumab, cetuximab and panitumumab can 

harm foetal development [2-5], handling guidelines are needed for 

pregnant or lactating hospital staff. Furthermore, because all mAbs 

are proteins they may cause sensitivity reactions. As yet, there is no 

way of establishing safe concentrations or MAC values of monoclonal 

antibodies for healthcare workers. Fortunately, when compared 

with classical chemotherapeutics, more stringent endogenous 

barriers exist against mAbs. Monoclonal antibodies have a 

relatively large molecular weight (about 150 kDa) and in the 

absence of special techniques such as microneedles or electroporation, 

are unable to pass the skin barrier [6]. Additionally, 

Monoclonal antibodies are extremely susceptible to denaturation 

induced by pH changes or gastrointestinal enzymes. Hence, oral 

Ann-Sophie Franki 

PharmD, PhD 

Kathleen Simons 

PharmD 

absorption of these molecules is 

highly unlikely, but the risk of pulmonary 

absorption of mAB-containing 

aerosols, e.g. those created 

during vial reconstitution using 

syringes and needles, cannot be 

fully excluded [7]. 

Finally, one needs to consider 

whether it is safe to use the same 

equipment to prepare mAbs and 

cytostatics. In theory, it is possi- 

ble that a safety cabinet or isolator could become contaminated 

with traces of chemotherapeutics [8-10] and if, for example, 

an infliximab infusion is prepared following a cytostatic compounding 

session, it may become cross-contaminated. Because 

drugs such as infliximab are generally administered on nononcological 

wards, this contamination may then spread to 

other hospital departments where personal protection measures 

are not as strict as those of the oncology ward. 

Risk assessment 

In The Netherlands, a mAb risk classification is currently 

being executed. Each drug is assessed using a standardised 

method that has been developed by an independent Dutch 

research institute (TNO, Dutch Institute for Applied Sciences), 

which includes an assessment of the drug’s carcinogenicity, 

teratogenicity, and other toxic properties. Each drug is classified 

in one of five groups, with the highest class 5 being the 

most hazardous and class 1 being considered harmless. 

Cytostatics often fall into class 5. To assess toxic effects, 

exposure limits, material safety data sheets, and preclinical 

and clinical studies are reviewed. Using this method, mAbs 

generally fall into class 3 or 4. 

Under Dutch national recommendations, compounding in a 

safety cabinet or isolator is recommended for class 4 compounds, 

whereas compounds regarded as class 3 require only 

the provision of personal protection (protective clothing and 

gloves). Thus far, five of the eighteen investigated mAbs have 

been deemed class 4 (alemtuzumab, bevacizumab, cetuximab, 

muromonab, panitumomab) and one (ibritumomab) has even 

been deemed class 5, based on its radioactivity. Further mAb 

classifications are listed in Table 1. 

In Germany, a risk assessment of the most frequently used 

mAbs has been published [11]. After a thorough investigation 

6 European Journal of Oncology Pharmacy • Volume 5 • 2011 • Issues 3-4 www.ejop.eu

Table 1: Risk assessment of monoclonal antibodies performed in The Netherlands 

Name Indication Chimeric-human Possible risk Conclusion - class 

Abciximab Trombocytaggregation inhibition Chimeric No 3 

Adalimumab Rheumatoid arthritis, Crohn’s disease Human Not likely 3 

Alemtuzumab Leukaemia Human Reprotoxicity, serious 4 

immuno suppression 

Basiliximab Organ transplants Chimeric Not likely 3 

Bevacizumab Colorectal/mamma carcinoma Human Embryotoxic 4 

Cetuximab Colorectal carcinoma Chimeric Embryotoxic 4 

Ibritumomab Non-Hodgkin’s lymphoma Human Radioactive 5 

Infliximab Rheumatoid arthritis, Crohn’s disease Chimeric Not likely 3 

Muromonab Organ transplants Human Carcinogenic 4 

Natalizumab Multiple sclerosis Human Not likely 3 

Omalizumab Asthma Human No 3 

Palivizumab Respiratory syncytial virus Human No 3 

Panitumumab Colorectal carcinoma Human Embryotoxic, decreased 4 

fertility 

Rituximab Non-Hodgkin’s lymphoma, Chimeric Not likely 3 

rheumatoid arthritits 

Trastuzumab Mamma carcinoma Human Not likely 3 

of all available safety data, the study concluded that mAbs 

should be handled as hazardous substances and prepared in 

safety cabinets using maximum personal protection—as 

described in German national regulations. 

Survey of practices across Europe 

To help us define a national guideline, we conducted an email 

survey amongst ESOP delegates. Thirty countries were 

approached, and completed questionnaires were received from 

20 country representatives: Belgium (2 respondents), Bosnia, 

Croatia, Cyprus, Czech Republic, Denmark, Estonia (2 

respondents), Finland, France, Germany, Hungary, Italy, 

Malta, Poland, Portugal, Slovenia, Spain, Switzerland, The 

Netherlands, Turkey. Two countries, Belgium and Estonia, 

provided two separate replies, resulting in a total of 22 completed 

questionnaires. 

The first question asked was ‘where and by whom in the hospital 

were mAbs prepared?’ In 17 cases (77%), they were prepared in 

the pharmacy, in four cases (18%) they were prepared on the wards 

by nurses, and in 0 cases (0%) they were prepared on the wards by 

pharmacy staff. In some instances, however, mAbs for chemotherapy 

patients were prepared in the pharmacy, but mAbs for all other 

patient types were prepared on the wards, see Figure 1. 

The second question asked was ‘what type of equipment was used 

in the preparation of mAbs?’ The vast majority of respondents (n 

= 15, 66%) used a safety cabinet. Five respondents (22%) reported 

using an isolator, and three respondents (14%) said no equipment 

or a crossflow cabinet was used, see Figure 2. 

The next set of questions concerned the use of separate equipment 

for mAb preparation in non-chemotherapy patients. We 

asked these questions to review the possibility of cross-contamination, 

e.g. traces of chemotherapy residues on infusions for 

patients with rheumatoid arthritis or Crohn’s disease. Because 

many ESOP members work in dedicated chemotherapy clinics, 

only nine respondents were able to answer these questions. Five 

respondents used a separate safety cabinet or isolator, and four 

respondents reported that mAbs and cytotoxics were prepared 

using the same equipment in non-chemotherapy patients. 

Respondents were also asked whether their compounding equipment 

was cleaned between mAb and chemotherapeutic use. Six 

respondents reported that such a procedure existed in their hospital, 

but 12 respondents reported that this was not the case. The 

other four respondents said this question was not applicable in 

their situation, mainly because they had separate equipment for 

these distinct procedures. 

The final question asked was ‘what type of transfer device was 

used when preparing mAbs?’, see Figure 3. Responses to this 

question were diverse. Five respondents used only needles, 

four respondents used only spikes, and three respondents used 

closed transfer systems. However, most respondents (n = 7) 

reported that they used a combination of these devices. 


7

Figure 1: Where mAbs are prepared 

in your hospital 


The results of our survey provided a clear impression of the 

variety of practice across Europe. In this respect, it was striking 

that in countries where two different hospitals completed 

the questionnaire, the responses also differed. This suggests 

that, in keeping with practice in The Netherlands, none of the 

surveyed countries have a broad consensus or guideline on this 

topic. 

Recommendations and QuapoS guidelines 

In 2008, an ESOP technical workshop was held in Hamburg, 

Germany, and the subject of preparing mAbs, chemotherapy, 

active vaccines, and gene medicine was discussed. This workshop 

provided some recommendations on the issue: 

• Cytotoxics and mAbs for cancer patients can be prepared 

using the same equipment. 

• Monoclonal antibodies for non-cancer patients that have 

cytotoxic, mutagenic or reprotoxic (teratogenic) activities 

(CMR), should be prepared using safety equipment (safety 

cabinet or isolator) but in a different one than that which is 

used for the preparation of chemotherapy. If this is not possible, 

an appropriate cleaning procedure before and after the 

preparation must be established. 

These recommendations are due to be incorporated in the next 

edition of the Quality Standard for the Oncology Pharmacy 

Service with Commentary (QuapoS). As a result of the Dutch 

risk assessment, we believe that this draft ESOP guidance is 

valid, but only for approximately one-third of mAbs, i.e. the ones 

that we believe have CMR activities, or that are suspected of 

being cytotoxic or teratogenic. In these cases, one should prepare 

the drugs in a safety cabinet or isolator, using spikes or closed 

devices, in line with the compounding practice for cytotoxics. 

Authors 

Mirjam Crul, PharmD, PhD 

Hospital Pharmacist 

Division of Clinical Pharmacy 

Onze Lieve Vrouwe Gasthuis 

9 Oosterpark 

NL-1090 HM Amsterdam, The Netherlands 

Figure 2: Type of equipment used 

when preparing mAbs 

Ann-Sophie Franki, PharmD, PhD 

Central Pharmacy 

Universitair Ziekenhuis Gent 

185 De Pintelaan 

BE-9000 Gent, Belgium 

Kathleen Simons, PharmD 

Hospital Pharmacist 

Division of Clinical Pharmacy 

Sint Elizabeth Ziekenhuis 

60 Hilvarenbeekse Weg 

NL-5022 GC Tilburg, The Netherlands 

Figure 3: Type of transfer device used 

when preparing mAbs 

mAbs: monoclonal antibodies; Grey dots represent countries that were approached through the ESOP forum but did not return a completed questionnaire. 

References 

1. Orthoclone OKT3, Summary of product characteristics. Janssen- 

Cilag, 2010. 

2. NIOSH. List of new FDA drugs and warnings fitting NIOSH criteria 

for hazardous drugs 2006. Available from: www.cdc.gov/niosh/docket/ 

archive/docket105.html 

3. Halsen G, Kramer I. Gefahrdungsbeurteilung monoklonaler antikorper 

der ATC klasse L01XC. Krankenhauspharmazie. 2009;30:441-53. 

4. Chakravarty EF, Murray ER, Kelman A, Farmer P. Pregnancy outcomes 

following maternal exposure to rituximab. Blood. 2011;117 (5):1499-506. 

5. Shrim A, Garcia-Bournissen F, Maxwell C, Farine D, Koren G. 

Trastuzumab treatment for breast cancer during pregnancy. Can Fam 

Physician. 2008;54(1):31-2. 

6. Mitragotri, S. Immunization without needles. Nat Rev Immunol. 

2005;5(12):905-16. 

7. Wang W, Wang EQ, Balthasar JP. Monoclonal antibody pharmacokinetics 

and pharmacodynamics. Clin Pharmacol Ther. 2008;84(5):548-58. 

8. Sessink PJ, Anzion RB, Van den Broek PH, Bos RP. Detection of 

contamination with antineoplastic agents in a hospital pharmacy 

department. Pharm Weekbl Sci.1992;14(1):16-22. 

9. Schulz H, Bigelow S, Dobish R, Chambers CR. Antineoplastic agent 

workplace contamination study: the Alberta Cancer Board Pharmacy 

perspective. J Oncol Pharm Pract. 2005;11(3):101-9. 

10. Mason HJ, Blair S, Sams C, et al. Exposure to antineoplastic drugs in two 

UK hospital pharmacy units. Ann Occup Hyg. 2005;49(7):603-10. 

11. Halsen G, Kramer I. Forschung BGW. Bewertung monoklonaler anti-korper 

zum schutz beschaftiger. 30 Oktober 2008. Available from: www.bgwonline.de 

bestellnummer EP- BmAk 




The role of a pharmacist according to patients 

From a patient’s point of view, pharmacists play a key role in the healthcare team through the provision of highquality 

medication, appropriate information on treatment schedules and effects of medication, as well as advice on 

the management of adverse events and use of complementary treatments. 

Introduction 

In recent years, substantial changes have been 

made to our approaches to healthcare provision. 

An increasing emphasis has been placed 

on a multidisciplinary approach to care, as 

well as treatment in the community setting. In 

addition, a substantial evolution in the way 

patients are involved in the management of their 

diseases (patient participation) has taken place. 

Many patients are keen to have an active say in 

their treatment and often look for additional 

material to supplement the information offered by their healthcare 

providers [1]. Indeed, a ‘new consumer’ has been described by 

pharmacists, predominantly young customers or the chronically ill, 

who are well informed, inquisitive, with a desire for longer 

dialogue and who ask critical questions and seek counselling [2]. 

Accordingly, the objective of patient management strategies has 

been defined to provide a patient-centred approach. 

The pharmacist plays a key role both as a partner within the healthcare 

team, actively involved in the delivery of care through the provision 

of high quality medication on the one hand, as well as being 

a source of appropriate information and education regarding 

treatment schedules, desirable effects, as well as side effects of 

medication and including advice on the management of adverse 

events. This demonstrates a substantial maturation in the role of the 

pharmacist. In the future, pharmacists may also play a greater role 

in the independent prescribing of medicines [3]. 

Overview: patient expectations 

Patients look to their pharmacist not as a salesperson, but as a 

skilled professional with up-to-date knowledge and expertise, 

to be able to offer appropriate advice and information both on 

general and specific health issues [4]. Key attributes of a pharmacist 

are respecting the privacy and confidentiality of 

patients, as well as offering compassion and empathy in discussions 

of their diseases, treatments or concerns, which highlights 

the importance of good communication and interpersonal 

skills [4-6]. Overall, in order to be beneficial, the relationship 

between pharmacists and patients needs to be built on 

mutual respect and trust. 

The results of a survey by Worley et al. which investigated the 

views of patient and pharmacist concerning the expectations 

both patients and pharmacists have of each other are revealing 

in this respect [7]. The survey employed a questionnaire to collect 

information on the following aspects: information sharing, 

responsible behaviour, interpersonal communication, creating 

a patient-centred relationship, and active communication relat- 

Anita Waldmann 

ed to health care. The study revealed that both 

patients and pharmacists have similar views 

about the pharmacist’s role in sharing information, 

such as how to look out for side effects 

and whether a co-administration of other medicines 

is feasible. However, patients agreed less on 

pharmacists’ responsible behaviour, which 

specifically concerned working with patients to 

meet their health needs. In addition, patients 

agreed less about the pharmacist’s role in creating 

a patient-centred relationship and interpersonal 

communications, which related to availability and approachability 

from a patient’s point of view. Although these responses highlight 

aspects of the patient–pharmacist relationship that may benefit 

from improvements, the results, which were derived from 

national random samples in the US, may not be representative of 

the situation in Europe and, in addition, changes are likely to 

have occurred since the publication of this study in 2007. 

Providing appropriate information and advice 

The amount of information following an initial diagnosis of a 

disorder can often be overwhelming and confusing for 

patients. In addition, the initiation of a new treatment, especially 

oral treatments, is accompanied by a host of questions 

and a thorough explanation of expected effects is invaluable. 

For many patients, the jargon used in package inserts can often 

be unclear and unsettling. In addition, patients may be reluctant 

about asking the treating physician for clarification. Here, 

pharmacists can play a key role in explaining relevant information 

and giving advice in plain language. This involves the 

clear communication of administration schedules, as well as 

effects of the treatment. In addition, pharmacists are able to 

provide tools to patients and their families to deal with side 

effects. A detailed explanation of possible symptoms and how 

these manifest themselves can greatly reassure patients and 

caregivers and reduce feelings of panic and powerlessness 

when they arise. Pharmacists can provide valuable education 


egarding steps that patients themselves can take to manage 

side effects, as well as outlining signals that indicate serious 

side effects, which would require further advice and intervention 

from healthcare professionals. Provision of such management 

information will empower patients, greatly contributing 

to a responsible approach to therapy. Assessment of risks and 

ensuring their safety is a key concern for patients [5]. 

In summary, pharmacists play important roles as educators and 

counsellors on specific disease and treatments issues. In addition, 

there are chronic disorders, such as diabetes, for which 

patients’ needs extend beyond advice on specific interventions 

to guidance on sustained lifestyle changes, an example that 

demonstrates the role of the pharmacist as an essential part of 

the interdisciplinary diabetes care team [8]. 

Providing information regarding complementary 

medicines 

Many patients are keen to supplement their treatments with complementary 

medicines, which they may not always disclose to 

their treating physician simply because they are not aware that 

negative drug interactions may arise [1]. Here, pharmacists can 

play a proactive and crucial role by asking about supplementary 

medicines and explaining the benefits, risks, and possible contraindications. 

Indeed, a survey conducted among Australian 

community pharmacies found that patients expect pharmacists to 

advise them on complementary medicines [1]. 

Providing information regarding patient support 

organisations 

Following the diagnosis of a serious or terminal illness, 

patients and families may feel isolated and confused and may 

benefit from contact with patients and caregivers in similar circumstances. 

Pharmacists are well placed to provide links or 

contact information for patient support organisations or other 

sources of information to assist patients and relatives with 

meeting other patients. 

Explanation of schedules and the importance of 

compliance 

Medication schedules can be a source of confusion for patients, 

particularly if a number of medications have to be taken which 

require particular times or circumstances, e.g. fasting versus 

administration with food. Pharmacists play a key role in explaining 

schedules of administration, thereby reinforcing the information 

provided by the treating physician, as well as being in a good 

position to stress the importance of adherence to treatment schedules 

to maximise the effects of therapy [9]. 

Non-compliance is recognised to be a frequent problem in the 

outpatient setting [10] and a number of factors specifically 

contributing to non-compliance with antibiotic therapy have 

been identified. These include the cost of drugs, formulation, 

rapid improvement of symptoms, forgetfulness, frequent dosing, 

complex regimens, side effects and patient beliefs [10]. 

Non-compliance is associated with serious consequences, such 

as patients receiving inappropriate doses of medication, thereby 

affecting clinical outcomes. In addition, there are significant 

cost implications, not only because of wasted medications, 

but due to additional examinations and interventions that 

have to be implemented [10]. 

Through regular contact with patients or their family members, 

pharmacists are uniquely placed to discuss and review feasible 

and meaningful goals of therapy with patients to meet their 

expectations and ensure compliance to treatment. 

Conclusion 

The role of the pharmacist has matured substantially over 

recent years to encompass not only the dispensing of medicine, 

but also a substantial involvement in disease management. 

Pharmacists play a key role in providing relevant information 

and advice on the practical aspects of treatment and are therefore 

essential partners in the multidisciplinary teams involved 

in the patient-centred provision of healthcare. The relationship 

between patients and pharmacists is therefore an integral 

aspect of ensuring patient welfare. 

Author 

Anita Waldmann 

Myeloma Euronet AISBL/Leukaemiehilfe Rhein-Main eV 

6 Falltorweg 

DE-65428 Ruesselsheim, Germany 

References 

1. Braun LA, Tiralongo E, Wilkinson JM, Spitzer O, Bailey M, Poole S, 

et al. Perceptions, use and attitudes of pharmacy customers on complementary 

medicines and pharmacy practice. BMC Complement 

Altern Med. 2010;10:38. 

2. Traulsen JM, Noerreslet M. The new consumer of medicine-the pharmacy 

technicians’ perspective. Pharm World Sci. 2004;26(4):203-7. 

3. Hobson RJ, Scott J, Sutton J. Pharmacists and nurses as independent 

prescribers: exploring the patient’s perspective. Family Practice. 

2010;27:110-20. 

4. Tinelli M, Bond C, Blenkinsopp A, Jaffray M, Watson M, Hannaford 

P; Community Pharmacy Medicines Management Evaluation Team. 

Patient evaluation of a community pharmacy medications management 

service. Ann Pharmacother. 2007 Dec;41(12):1962-70. 

5. Futter B. The naked patient. S Afr Pharm J. 2011;78(2):56. 

6. Naik Panvelkar P, Armour C, Saini B. Community pharmacy-based 

asthma services-what do patients prefer? J Asthma. 2010;47(10): 

1085-93. 

7. Worley MM, Schommer JC, Brown LM, Hadsall RS, Ranelli PL, 

Stratton TP, et al. Pharmacists’ and patients’ roles in the pharmacistpatient 

relationship: are pharmacists and patients reading from the 

same relationship script? Res Social Adm Pharm. 2007;3(1):47-69. 

8. Sisson E, Kuhn C. Pharmacist roles in the management of patients 

with type 2 diabetes. J Am Pharm Assoc. 2009;49(Suppl 1):S41-5. 

9. Vivian EM. The pharmacist’s role in maintaining adherence to insulin therapy 

in type 2 diabetes mellitus. Consult Pharm. 2007 Apr;22(4):320-32. 

10. Kardas P, Bishai WR. Compliance in anti-infective medicine. Adv 

Stud Med. 2006;6(7C):S652-8. 


11



Companion diagnostics and personalised cancer 

medicine 

Cancer is a heterogeneous disease that requires an individualised treatment approach. Drug treatments guided 

by molecular diagnostic testing are increasingly being used in the clinic. This article shows that the concept 

of stratified cancer medicine has become a reality. 

Introduction 

Our increased molecular understanding of 

human diseases will change the way that 

drugs are developed and how pharmacotherapy 

is practiced in the years to come [1, 2]. 

We know that most diseases are heterogeneous 

and that they can be divided into biological 

subgroups, each requiring a specific 

therapeutic intervention. When it comes to 

individualisation of pharmacotherapy, oncol- Jan Trøst Jørgensen 

ogy has been at the forefront and a number of MScPharm, PhD 

drugs have already been developed based on 

a detailed molecular knowledge of the disease mechanisms [3]. 

Personalised and stratified medicine 

When we talk about individualising pharmacotherapy we often use 

expressions like ‘tailored therapy’ or ‘personalised medicine’, 

which may give the impression of a totally individualised pharmacotherapy 

like ‘targeting drugs for each unique genetic profile’ [4]. 

However, this is yet far from being a reality. What we experience 

right now, and will continue to experience much more in the years 

to come, is that by using molecular diagnostic tests we will be able 

to divide the patients who ‘share’ molecular biological characteris- 

Table 1: Drugs for the treatment of solid tumours where companion 

diagnostic tests are used 

Maria Hersom 

BSc 

Drug Indication Biomarker 

Tamoxifen (Nolvadex, AstraZeneca) Breast cancer ER 

Letrozole (Femara, Novartis) Breast cancer ER 

Anastrozole (Arimidex, AstraZeneca) 

Exemestane (Aromasin, Pfizer) 

Trastuzumab (Herceptin, Roche) Breast cancer HER2/HER2 

Gastric cancer HER2/HER2 

Lapatinib (Tykerb, GlaxoSmithKline) Breast cancer HER2/HER2 

Epirubicin (Ellence, Pfizer) Breast cancer TOP2A 

Doxorubicin (Adriamycin, Pfizer) 

Cetuximab (Erbitux, Colorectal cancer EGFR/KRAS 

Bristol-Myers Squibb/Merck) 

Panitumumab (Vectibix, Amgen) Colorectal cancer EGFR/KRAS 

Gefitinib (Iressa, AstraZeneca) Non-small cell lung EGFR 

cancer 

Erlotinib (Tarceva, Roche) Non-small cell lung EGFR 

cancer 

Imatinib (Glivec, Novartis) Gastrointestinal C-KIT (CD117) 

stromal tumour 

Vemurafenib (Zelboraf, Plexxicon/Roche) Melanoma BRAF V600E 

tics into subgroups and, based on this information, 

we can match these patients with 

the right drug. In this situation, the 

molecular diagnostics serve as a stratification 

test, which has led to the use of the 

expressions ‘stratified medicine’ or ‘stratified 

pharmacotherapy’. Stratified medicine 

has been defined as follows: management 

of a group of patients with 

shared biological characteristics by using 

molecular diagnostic testing to select the 

most optimal therapy in order to achieve 

the best possible medicinal outcome for that group [5]. 

Companion diagnostics 

The molecular diagnostics tests used in stratified cancer medicine 

rely on different technologies and the dominating analytical methods 

are immunohistochemistry (IHC), fluorescence in situ hybridisation 

(FISH), chromogenic in situ hybridisation (CISH), and 

reverse transcription-polymerase chain reaction (RT-PCR) [3]. 

When these molecular diagnostics tests are used in combination 

with drugs they have been given a specific name. Initially, these 

tests were called pharmacodiagnostics or theranostics, but within 

the last 3–5 years the expression ‘companion 

diagnostics’ has taken over. A companion diagnostics 

is defined as: a pre-treatment test performed 

in order to determine whether or not a 

patient is likely to respond to a given therapy. 

This type of test is classified as a predictive test 

and a prerequisite for implementation of stratified 

and personalised medicine [5]. 

A number of drugs are listed in Table 1 for the 

treatment of solid tumours where the clinical 

use is guided by a companion diagnostic test. 

For several of these drugs, it is a requirement 

that companion diagnostic testing is performed 

before they can be prescribed to the patient. 

Stratified cancer medicine 

Breast cancer, like most other cancers, is a disease 

where heterogeneity exists and where the 

principle of stratified medicine has in fact been 

practised for the last couple of decades. This 

already began in the 1970s with the development 

of the first selective oestrogen receptor 


modulator tamoxifen. Tamoxifen was developed for women with 

oestrogen receptor positive breast cancer, which make up approximately 

60–70% of the population with the disease [6]. From a 

phase II study with tamoxifen performed in patients with advanced 

breast cancer, published in 1976, it was concluded: a high degree of 

correlation between response and positive estrogen-receptor assay 

suggests the value of the diagnostic test as a means to select patients 

for tamoxifen treatment [7]. For the first time, we have a combination 

of a targeted drug and a predictive diagnostic assay/companion 

diagnostic test. Despite the fact that this study was published 35 

years ago, the conclusion about combining drug and diagnostics 

seems more relevant than ever. 

Late in the 1990s another example appeared, in fact the one which 

is most often referred in relation to personalised or stratified medicine, 

the combination of the IHC diagnostic test for HER2 and the 

monoclonal antibody trastuzumab. Trastuzumab targets the extracellular 

domain of HER2 and the effect is dependent on overexpression 

of the HER2 protein, or amplification of the HER2 gene, which 

is tested for by IHC or FISH, respectively [3, 8]. These protein or 

gene changes occur in 20–25% of all women with breast cancer, 

and it is in this subset of patients that trastuzumab has shown to be 

effective [9, 10]. Recently, trastuzumab has also proven to be effective 

in advanced gastric cancer, especially in the subgroup of 

patients that had the highest overexpression of the HER2 protein 

[11]. When it comes to HER2 positive breast cancer, a number of 

monoclonal antibodies and tyrosine kinase inhibitors have been 

developed or are under development, such as lapatinib, neratinib 

(Pfizer), and pertuzumab (Roche/Genentech), so the treatment of 

this patient group may be even more effective in the future [12, 13]. 

Just as the development of trastuzumab must be regarded as a major 

breakthrough in the treatment of breast cancer, a new breakthrough 

seems to be under way in relation to the treatment of metastatic 

melanoma, where no effective treatment has so far been available. 

Very recently, promising interim phase III data with vemurafenib 

(Plexxicon/Roche) has been published [14]. Vemurafenib is a B- 

RAF kinase inhibitor that selectively blocks the RAF/MEK/ ERK 

pathway in BRAF V600E mutated cells [15]. It is estimated that 

approximately 40–60% of the melanoma patients have this type of 

BRAF mutation, which is measured by RT-PCR. In the phase III 

study vemurafenib was compared to dacarbazine in metastatic 

melanoma patients with the BRAF V600E mutation. The efficacy of 

vemurafenib was dramatically improved compared to dacarbazine, 

with a response rate of 48% for the patients treated with vemurafenib 

and only 5% for the dacarbazine group. The treatment with 

vemurafenib was further associated with a relative reduction of 

64% in the risk of death and a 74% reduction in the risk of disease 

progression compared with dacarbazine [14]. This data must be 

considered a major step forward in the treatment of this highly 

deadly disease and it will be interesting to see what the effect will 

be on the median overall survival when the study is finally concluded. 

Based on the recent phase III data, the FDA has (on 17 August 

2011) approved vemurafenib for the treatment of metastatic and 

unresectable melanomas together with the companion diagnostic 

test for BRAF V600E mutation. 

Conclusion 

If medical anticancer treatment is to be improved, disease heterogenecity 

must be taken into account when drugs are developed and 

subsequently used in the clinic. The drug-diagnostic co-development 

model has already proven its value with drugs like tamoxifen, 

trastuzumab, imatinib, and now also with vemurafenib. The use of 

companion diagnostics will be a decisive factor in utilising the clinical 

potential of the new targeted anticancer drugs to the benefit of 

patients. 

Authors 

Jan Trøst Jørgensen, MScPharm, PhD 

Dx-Rx Institute 

76 Baunevaenget 

DK-3480 Fredensborg, Denmark 

Maria Hersom, BSc 

Human Biology 

Faculty of Health Sciences 

University of Copenhagen 

DK-2200 Copenhagen, Denmark 

References 

1. Jørgensen JT. From blockbuster medicine to personalized medicine. Per 

Med. 2008;5:55-63. 

2. Collier R. Bye, bye blockbusters, hello niche busters. CMAJ. 

2011;183(11):E697-8. 

3. Jørgensen JT, Nielsen KV, Ejlertsen B. Pharmacodiagnostics and targeted 

therapies - a rational approach for individualizing medical anti-cancer therapy 

in breast cancer. Oncologist. 2007;12:397-405. 

4. Langreth R, Waldholz M. New era of personalized medicine - targeting 

drugs for each unique genetic profile. Oncologist. 1999;4:426-7. 

5. Jørgensen JT. Are we approaching the post blockbuster era? 

Pharmacodiagnostics and rational drug development. Expect Rev Mol 

Diagn. 2008;8(6):689-95. 

6. Cheung KL. The estrogen and progesterone receptors - setting the scene for 

pharmacodiagnostics. In: Jørgensen JT, Winther H, editors. Molecular diagnostics 

- the key driver of personalized cancer medicine. Singapore: Pan 

Stanford Publishing; 2010. p. 21-42. 

7. Lerner HJ, Band PR, Israel L, et al. Phase II study of tamoxifen: report of 

74 patients with stage IV breast cancer. Cancer Treat Rep. 

1976;60(10):1431-5. 

8. Jørgensen JT, Møller S, Rasmussen BB, et al. High concordance between 

two companion diagnostics tests: a concordance study between the 

HercepTest and the HER2 FISH pharmDx Kit. Am J Clin Pathol. 

2011;136: 145-51. 

9. Slamon DJ, Leyland-Jones B, Shak S, et al. Use of chemotherapy plus a 

monoclonal antibody against HER2 for metastatic breast cancer that overexpresses 

HER2. N Engl J Med. 2001 Mar;344(11):783-92. 

10. Gianni L, Dafni U, Gelber RD, et al. Treatment with trastuzumab for 1 year 

after adjuvant chemotherapy in patients with HER2-positive early breast 

cancer: a 4-year follow-up of a randomised controlled trial. Lancet Oncol. 

2011 Mar;12(3):236-44. 

11. Jørgensen JT. Targeted HER2 treatment in advanced gastric cancer. 

Oncology. 2010;78(1):26-33. 

12. Roy V, Perez EA. Beyond trastuzumab: small molecule tyrosine kinase inhibitors 

in HER-2 positive breast cancer. Oncologist. 2009;14(11):1061-9. 

13. Lee-Hoeflich ST, Crocker L, Yao E, et al. A central role for HER3 in 

HER2-amplified breast cancer: implications for targeted therapy. Cancer 

Res. 2008 Jul;68(14):5878-87. 

14. Chapman PB, Hauschild A, Robert C, et al. Improved survival with vemurafenib 

in melanoma with BRAF V600E mutation. N Engl J Med. 2011 

Jun;364(26):2507-16. 

15. Bollaf G, Hirth P, Tsai J, et al. Clinical efficacy of a RAF inhibitor needs 

broad target blockade in BRAF-mutant melanoma. Nature. 2010 

Sep;467(7315):596-9. 


13

Introduction 

Oncology is currently the fastest 

growing therapeutic area, and an 

increasing number of clinical 

trials are being conducted. 

Clinical trial management provides 

an excellent example of a 

multidisciplinary team approach. 

Indeed, the clinical research 

team will involve the sponsor, 

frequently its clinical research 

organisation (CRO) and devel- 



An assessment of the pharmacist’s role in 

oncology trial management 

This article reports on a ESOP survey which was undertaken to gather information about the current involvement 

of oncology pharmacists in clinical trial management across Europe. Significant differences in national 

practices are also highlighted and potential standardisation solutions are suggested. 

Mikael Daouphars 

PharmD, PhD 

opment specialists, the principal investigator and doctors, clinical 

research assistants and possibly research nurse(s), pharmacists, 

laboratory technicians and perhaps social workers. 

The pharmacist has become an integral part of the clinical 

research team. As a drug expert, he is the right person to 

manage all of the trial’s drug-related activities, thereby contributing 

to the overall smooth running of the study. 

Management of clinical trials in oncology 

By participating in clinical trials in oncology, the clinical pharmacist 

contributes to quality assurance. QuapoS 4 provides a 

reference guideline to be used to organise pharmacist-driven 

activities that are related to clinical trials [1]. On the basis of 

all applicable legal regulations, services that the pharmacist 

could provide in a clinical trial setting are: 

• investigational drugs ordering 

• shipment reception 

• storage 

• adequate labelling according to EU legislation if not previously 

realised by the sponsor 

• randomisation 

Ewelina Korczowska 

MPharm 

Martin Sevec 

PharmD 

• preparation of drugs, and eventual 

blinding 

• dispensing 

• return or disposal of used 

/unused investigational drugs. 

Pharmacists may also become 

involved in studies that investigate 

a drug’s stability, and the 

acceptance of patients who are 

selected to be enrolled on the clinical 

trial. Careful documentation 

of each of these steps in the clinical trial’s file is mandatory. 

European survey 

The role of pharmacy as a profession in the clinical research field 

needs to be fully understood. In recent years, European law has 

increasingly been implemented in national pharmaceutical law. 

However, practices can differ from one European country to 

another, as a result of differing legal regulations or historical pharmacy 

involvement. A study was therefore developed by ESOP to: 

• gather information about the current involvement of oncology 

pharmacists in clinical trial management in Europe 

• better clarify the level of pharmacy activities related to clinical 

trials in different European countries 

• identify appropriate actions to improve current standings. 

Methodology 

A short questionnaire was developed by three European pharmacists. 

All questions concerned pharmacist-related tasks 

during clinical trials, see Questionnaire. The questionnaire was 

circulated to all ESOP members with their online membership 

letter. It was also available on the ESOP website. Answers 

were collected from 21 December 2010 to 10 January 2011. 

Figure 1: Profile of hospital respondents Figure 2: Number of oncology clinical trials 

University hospital 

General hospital 

Oncology hospital 

< 30 

30–50 

50–75 

75–100 

100–150 

> 150 


Questionnaire 

Tasks: medication/ancillaries order; cool chain medication 

transport verification; shipment delivery confirmation; temperature 

controlled medication storage; inventory review; 

medication preparation; billing; waste management including 

used medication containers destruction, expired medication 

destruction; communication with sponsor/CRO – monitoring 

visit, discrepancy reports, changes establishment; +/- subject 

randomisation; +/- medication reallocation. 

1. Name tasks different from the above mentioned that 

should/should not be your own. Does reality in your 

pharmacy overlap your opinion? 

2. Do you have independent ‘Department for clinical trial 

management’ or independent ‘Employee for clinical trial 

management’ in your pharmacy? If yes, what is its/his(her) 

scope (please specify in detail)? 

3. Do you have in your pharmacy transparent system of 

rewarding clinical trial staff according to its study workload? 

(In case you have independent ‘Department for clinical trial 

management’ or independent ‘Employee for clinical trial 

management’ in your pharmacy is it so all pharmacy 

employees are rewarded ‘equally’ taking into account their 

casual workload or those involved in clinical trial management 

are given an advantage over others?) 

4. Do you find better paper records or electronic ones (IVRS, 

IWRS)? Do you think they both have to be done or one is 

enough? Which one and why should then be preferred? 

5. Comparing clinical trial management with standard work 

do you think you need closer cooperation than just routine 

one with MDs (PI, subinvestigators) (please specify in 

detail)? 

6. When having a combination of orally medication and 

parenteral chemo in a single clinical trial do you in 

chemounits deal with orally medication as well or do you 

deal with parenteral chemo only and orally taken one is 

someone else responsibility (please specify in detail)? 

This questionnaire is the original version produced by the authors. 

PI: principal investigator. 

The completed questionnaires were returned by fax or were 

emailed as a PDF file. 

Results 

The results from each question have been analysed separately 

in order to highlight any differences or similarities between 

each European country. However, they have been presented 

holistically here for simplicity. Collected data can only be 

taken as an illustration of the current situation for the responding 

pharmacy. It cannot be taken as representative of the current 

situation for each European country in general. 

Thirty-seven completed questionnaires were received from 16 

European countries. Germany had the highest proportion of 

respondents (40% of the total). Approximately half of the 

respondents worked in general hospitals, one-third were from 

university hospitals, and only 8% were from specialist oncol- 

Table 1: Services provided by the pharmacy (% of 

respondents) 

100% 

Cool chain medication transport verification 

Shipment delivery confirmation 

Temperature controlled medication storage 

Medication preparation 

75–100% 

Inventory review 

Communication with sponsor/CRO 

Monitoring visit 

Medication order 

Waste management 

Expired medication destruction 

Expired/unused medication delivery to sponsor 

Discrepancy report 

50–75% 

Co-management of all ongoing hospital clinical trials 

Billing 

Relabelling 

Changes establishment 

25–50% 

Randomisation 

Medication reallocation 

Independent department for clinical trial management 

Transparent rewarding system 

ogy hospitals, see Figure 1. Most respondents (76%) had been 

involved with up to 50 clinical trials, see Figure 2. 

The pharmacy ward was involved in clinical trial management 

in 95% (n = 35) of the respondents’ hospitals. Pharmacy technicians 

were involved in approximately half of the hospitals. 

The mean number of pharmacists per hospital involved in each 

trial was between two and three, and between three and four 

for pharmacy technicians. 

Services provided by the pharmacy in relation to clinical trials 

are detailed in Table 1. There were few differences 

between countries, apart from relabelling, randomisation and 

medication reallocation. Billing was not systematic, and a 

transparent reward system was only reported by 25–50% of 

respondents. However, these relatively low figures do not 

mean that reward systems are generally absent. If the pharmacy 

staff are rewarded from the trial budget, the reward is 

shared equally without considering individual clinical trial 

management involvement. 

Electronic records of data were usually preferred by respondents 

over paper records, especially interactive internet web 

response services (IWRS). However, both paper and electronic—IVRS 

(interactive voice response systems)/IWRS—were 

often required by the sponsor. 

Discussion and conclusion 

Many oncology pharmacists currently operating in Europe 


15



have extensive clinical trial management experience. This contribution 

has been widely recognised, with some tasks that have 

fallen to doctors now being allocated to the pharmacist. 

However, a transparent and equitable reward scheme for pharmacy-related 

tasks still needs to be standardised between countries. 

Communication between pharmacists and sponsors’ clinical 

research assistants could also be improved with regard to specific 

pharmacy-related tasks, especially the preparation of new 

drugs. The application of European regulations, along with the 

implementation of QuapoS recommendations and the collaboration 

of European pharmacists should help to standardise practice. 

Author for correspondence 

Mikael Daouphars, PharmD, PhD 

Pharmacy 

Cancer Centre Henri Becquerel 

Breast cancer radiotherapy is now 

established as a viable therapeutic 

strategy on a par with 

chemo- or hormone therapy. 

Principally, this is because lymph 

node-positive tumour irradiation not only 

reduces the frequency of tumour recurrence, 

but also improves overall survival. Modern 

irradiation technology is also now associated 

with fewer tolerability issues when compared 

with older radiotherapy techniques. 

There are also new recommendations regarding ductal carcinoma 

in situ (DCIS), specifically that radiotherapy is not necessary 

in the case of small malignant cells (< 2 cm), free resection 

margins (> 10 mm), and favourable gradings [1]. 

Furthermore, radiotherapy with N+/- status has a positive 

effect on overall survival and recurrence reduction after both 

1 rue d’Amiens 

FR-76000 Rouen, France 

Co-authors 

Ewelina Korczowska, MPharm 

Przemienienie Panskie Clinical Hospital 

University of Medical Sciences 

Poznan, Poland 

Martin Sevec, PharmD 

University Hospital Motol 

Prague, Czech Republic 

Reference 

1. van Gemmern R. Quality standard for the oncology pharmacy services 

with commentary (QuapoS 4), 2008. 

Breast cancer irradiation: 2011 update 

Several developments have recently emerged in the field of breast cancer radiotherapy. This article summarises 

those that most impact pharmacists. 

Professor Dr Wolfgang Wagner 

MD, PhD 

mastectomy and breast-conservation surgery, 

see Figure 1 [2]. 

To date, physicians have been cautious when 

indicating radiotherapy in patients with breast 

reconstructions immediately following mastectomy. 

This is because of a fear of implant failure. 

A recent study by Ho et al. has indicated 

that under certain circumstances, early radiotherapy 

may be possible despite implants—the 

trial showed a rate of removal of implants/ 

replacements of 21% after seven years [3]. 

The success of radiotherapy depends on the interval between 

surgery and the start of irradiation, a systematic review has 

suggested that this period should be a maximum of eight 

weeks, see Figure 2 [4]. Existing treatment programmes 

include primary chemotherapy, which can lead to a delay of 

Figure 1: Radiotherapy outcomes according to node status Figure 2:Associations between delay in postoperative radiotherapy 

for breast cancer and local recurrence rates 


Figure 3: Radiotherapy outcome versus tumour characteristics 

radiotherapy administration such that the risk of local recurrence 

is increased considerably, especially with regard to small 

tumour-free resection margins. 

Partially accelerated breast irradiation—total dose given within 

one week—is not yet considered standard therapy, whilst intraoperative 

radiotherapy is still regarded as being in an experiemental 

phase. Follow-up currently spans only two years, meaning that 

results cannot be conclusively evaluated, even though the 

observed local tumour control is comparable with the established 

procedure and toxicity appears to be lower. 

The results of radiotherapy depend on the tumour’s molecular 

characteristics cf. chemotherapy. In fact, when certain molecular 

characteristics are present, radiotherapy can be a disadvantage 

for the patient, see Figure 3 [5]. 

Conclusion 

Breast cancer radiotherapy not only evokes local tumour con- 

Extravasation of cytotoxics: there is still room for improvement 

References (please see article on pages 18–19) 

1. Mader I, Furst-Weger P, Mader RM, Nogler- 

Semenitz E, Wassertheurer S. Extravasation of 

cytotoxic agents, 2nd edition. Wien New York: 

Springer; 2010. 

2. Parikh P, Pai VP, Ranjan S, Swami A, 

Cuchelkar V, Agarwal P, et al. Phlogenzym is 

safe and effective in reducing morbidity of 

vesicant chemotherapy extravasation - a 

prospective study. Int J Immunother. 2001; 

17(2-4):163-70. 

3. Langer SW, Sehested M, Jensen PB. Treatment 

Hospital workers perceptions about nano-technology 


1. Siegrist M, Wiek A, Helland A, Kastenholz H. 

Risks and nanotechnology: the public is more 

concerned than experts and industry. Nat 

Nanotechnol. 2007 Feb 2 [cited 2011 Sep 28]. 

Available from: www.nature. com/naturenanotechnology 

2. Toumey C. Rules of engagement. Nat Nanotechnol. 

2007 Jul 2 [cited 2011 Sep 28]. Available 

from: www.nature.com/naturenanotechnology 

of anthracycline extravasation with dexrazoxane. 

Clin Cancer Res. 2000;6:3680-6. 

4. Laurie SW, Wilson KL, Kernahan DA, 

Bauer BS, Vistnes LM. Intravenous extravasation 

injuries: the effectiveness of hyaluronidase 

in their treatment. Ann Plast Surg. 

1984;13:191-4. 

5. Mouridsen HT, Langer SW, Buter J, Eidtmann 

H, Rosti G, de Wit M, et al. Treatment of 

anthracycline extravasation with Savene (dexrazoxane): 

results from two prospective clinical 

3. Cobb M, Macoubrie J. Public perceptions about 

nanotechnology. Risks, benefits and trust. J 

Nanopart Res. 2004;6(4):395-405. 

4. Scheufele D, Lewenstein B. The public and nanotechnology: 

how citizens make sense of emerging 

technologies. J Nanopart Res. 2005;7:659-67. 

5. Currall SC. Nanotechnology and society new 

insights into public perceptions. Nat Nanotechnol. 

2009 Feb 4 [cited 2011 Sep 28]. Available from: 

www.nature.com/naturenanotechnology 

trol, but in certain circumstances, it can also extend overall 

survival. New irradiation technologies and programmes are 

likely to further improve results. 

Author 

Professor Dr Wolfgang Wagner, MD, PhD 

Professor of Radiotherapy 

Department of Radiotherapy 

Paracelsus Strahlenklinik Osnabrück 

69 Am Nantruper Holz 

DE-49076 Osnabrück, Germany 

References 

1. AGO Leitlinien 2010. AGO therapy guidelines ‘Breast Cancer’. 

Guidelines for diagnosis and treatment of breast cancer (Empfehlung 

seit 2002). Available from: www.ago-online.org 

2. McGale P, Darby S, Taylor C, Peto R. The 2006 worldwide overview 

of the effects of local treatments for early breast cancer on long-term 

outcome. Int J Radiat Oncol Biol Phys. 2006 Nov 1;66(3):S2-S3. 

3. Ho AY, Cordeiro P, Wright J, et al. Favorable long-term outcomes are 

achievable in women with immediate permanent implant breast reconstruction 

and postmastectomy radiation. Int J Radiat Oncol Biol Phys. 

2010 Nov 1;78(3):S3. 

4. Huang J, Barbera L, Brouwers M, Browman G, Mackillop WJ. Does 

delay in starting treatment affect the outcomes of radiotherapy? A systematic 

review. J Clin Oncol. 2003 Feb 1;21(3):555-63. 

5. Kyndi M, Sørensen FB, Knudsen H, Overgaard M, Nielsen HM, 

Overgaard J, et al. Estrogen receptor, progesterone receptor, HER-2, 

and response to postmastectomy radiotherapy in high-risk breast cancer: 

the Danish Breast Cancer Cooperative Group. J Clin Oncol. 2008 

Mar 20;26(9):1419-26. 

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6. Bertelli G, Gozza A, Forno GB, Vidili MG, 

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for the prevention of soft tissue 

injury after extravasation of vesicant cytotoxic 

drugs: a prospective clinical study. J Clin 

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8. Kahan DM, Braman D, Slovic P, Gastil J, Cohen 

G. Cultural cognition of the risks and benefits of 

nanotechnology. Nat Nanotechnol. 2009;4(2): 

87-90. 


17



Extravasation of cytotoxics: there is still room 

for improvement 

Introduction 

Extravasation of vesicant cytotoxics still remains a major challenge. 

In contrast to many expectations, the use of classic cytotoxic 

agents has actually increased in the ‘era’ of targeted therapies. 

Patients, nowadays, frequently experience fourth- and fifth-line 

treatments and enjoy longer survival and a decrease in cancer 

mortality rates. Thus, an individual patient receives many more 

IV infusions than two decades ago. This fact explains why 

extravasation is not a fading memory, but a reality that is here to 

stay in the years to come. To face extravasations, this article does 

not summarise the management procedures already outlined 

extensively in several excellent reviews and books [1], but instead 

proposes actions aimed at quality management and to discuss 

open scientific issues, which need to be urgently addressed. These 

suggestions include establishing an ‘Extravasation Task Force’ in 

your hospital to deal with the implementation of quality control 

and knowledge management. 

Risk factors for extravasation 

Several antineoplastic agents are associated with toxicity to cutaneous 

and subcutaneous tissue. The most common risk factors 

concern patient-associated and iatrogenic risk factors. With the 

hazard of irreversible complications after extravasation, prevention 

is of the utmost importance. A classification of antineoplastic 

agents addresses potential tissue damage: vesicant, irritant, and 

non-vesicant. Depending on the extravasated agent, a sequence of 

emergency measures need to be followed, which is best done by 

adhering to a standard operation procedure (SOP). There is good 

evidence for the successful use of antidotes for some antineoplastic 

agents. These antidotes are dimethylsulfoxide or 

hyaluronidase, often combined with topical measures such as 

cooling or application of heat, whereas the use of the anthracycline 

antidote dexrazoxane is still a matter of controversial discussion. 

Most relevant, novel compounds are poorly characterised 

regarding their toxic potential and are therefore to be considered 

as major drug-associated risks until clinical data are available. 

Building a task force in the institution 

There are several good arguments to concentrate expertise and 

action in a task force: 

• Splitting interventions between different departments and disciplines 

can result in contradictory measures and irreproducible 

management standards within one institution 

• Hardly comparable documentation 

• Expertise varies within departments that administer cytotoxics, 

Ursula Pluschnig, MD; Shahla Farokhnia, aHPh; Gunar Stemer, aHPh; Professor Robert M Mader, DSc 

As many patients receive more intravenous therapies than before, extravasation is a challenge that is here to 

stay for the foreseeable future. This article outlines several proposals for an improved quality management 

of these issues and discusses the science behind them. 

e.g. oncologic wards versus clinical units that occasionally 

handle infusions of cytotoxics. 

A possible approach is the formation of interdisciplinary clinical 

working groups with the following tasks: 

1. Members of the task force are the first port of call within the 

hospital 

2. Coordination of the subsequent treatment stages including the 

consultation of plastic surgeons 

3. In regular meetings (similar to a tumour board) the group 

members discuss individual cases of extravasation with the 

aim to define SOPs 

4. Training of hospital staff 

5. Dissemination of results by publication of novel data. 

Since the start of the task force at the Medical University of 

Vienna and the Vienna General Hospital in 2006, more than 

200 cases have been managed proving its usefulness and 

allowing the accumulation of the necessary expertise in a large 

hospital within very few years. According to our experience, 

the working group should include members from the disciplines 

of oncology, plastic surgery, oncology pharmacy, clinical 

pharmacology, pathology, nursing, and (as required) physiotherapy. 

Given the pharmacological expertise of hospital 

pharmacists working in oncology, they may provide valuable 

contributions to extravasation management, when physicians 

and nursing staff are in urgent need of support. It is a rewarding 

opportunity to further engage in interdisciplinary clinical 

activities for the patient’s benefit. 

Training staff members 

Regular training sessions help to raise awareness in the institution’s 

clinical members, medical, and nursing staff. Most 

importantly, they impart knowledge concerning a rapid, qualified, 

and appropriate intervention in a situation close to emergency. 

Documentation, documentation, documentation ... 

Standardised documentation is crucial to follow and evaluate the 

measures taken, possible sequelae and the final outcome. It is 

good practice to use one of the available documentation sheets 

accessible via the Internet, e.g. www.paravasate.at, offering forms 

in both English and German. Documentation in the minimal version 

includes description of the event, symptoms, measures taken, 

sequelae, and aftercare. 


Knowledge management 

Due to the lack of prospective clinical studies on extravasation of 

cytotoxic drugs, our current knowledge has to rely on individual 

case reports and animal studies. As this situation is not subject to 

change in the near future, creating evidence by adherence to SOP 

and stringent documentation is the hard way to overcome the current 

stagnation in this field. 

The science behind extravasation 

The type of damage associated with cytotoxic agents is a central 

issue, becoming prominent with every new, registered substance. 

Even the relatively simple classification into three types of damage 

is sometimes difficult, let alone to propose more sophisticated 

sub-classifications, e.g. addressing the fact that the vesicant 

potential of paclitaxel is not comparable to that of anthracyclines. 

After extravasation of vesicants, the clinical course and extent of 

damage can hardly be predicted. This is particularly true for anthracyclines, 

when necroses can develop even weeks after extravasation. 

Despite extensive pharmaceutical and pharmacological knowledge, 

there is no reliable method to predict tissue toxicity on the basis of 

physicochemical characteristics. Even when similar compound 

structures may be a helpful hint—as for the vinca alkaloids and the 

anthracyclines, clinical confirmation is always required. 

As extravasations are not always noticed immediately, a time delay 

longer than five days often elapses [2]. This immediately raises the 

question of the time period allowed before the efficiency of antidotes 

is compromised. Established antidotes have been tested for 

their use immediately after the extravasation event. Dexrazoxane 

was active against anthracyclines for at least three hours after the 

extravasation event, but activity was clearly reduced for daunorubicin 

after six hours [3]. Even shorter time windows seem to apply 

for the antidote hyaluronidase [4]. For this reason, instruction of 

patients and regular monitoring of IV infusions is of such crucial 

importance: early detection enables us to use instruments when 

time is the most critical factor for effectiveness. 

As dexrazoxane has been approved based on the data from two single-arm 

studies [5], it is not clear how its efficacy compares with that 

of the highly established clinical use of topical cooling dimethyl sulfoxide 

(DMSO), which has also been tested in a prospective clinical 

trial with a very similar rate of success [6]. This serious flaw in the 

study design makes it difficult to draw definite conclusions. 

Pathological changes within the affected tissue have been poorly 

characterised so far. Although many authors know that inflammatory 

processes are not the primary event after extravasation, it 

would be very useful to understand the histopathological changes 

in the skin in order to limit the use of corticosteroids, which are 

still frequently administered without real evidence. 

New therapeutic entities 

The pharmacological landscape has changed fundamentally over 

the last ten years and new oncology pharmacotherapy options will 

continue to emerge. With the introduction of mitosis-interfering 

compounds eribulin and vinflunin, two new chemical entities 

with novel mechanisms of actions, limited clinical experience and 

toxicological data enlarged the armamentarium of physicians. To 

date, few data regarding substance-specific risks and management 

procedures following extravasation exist. In the absence of conclusive 

data, the vesicant or irritant potential of new compounds 

can only be indirectly deduced from parameters such as structureactivity 

relationship and formulation characteristics (pH value, 

excipients, osmolarity of the infusion solution). 

At the same time, new galenic formulations of well-established 

compounds, e.g. liposomal daunorubicin and doxorubicin, and protein-bound 

paclitaxel are increasingly used due to decreased local 

and systemic toxicity compared to their non-modified precursors. 

Several monoclonal humanised antibodies, e.g. rituximab, 

trastuzumab, bevacizumab, cetuximab, panitumumab, and others, 

have become essential in the treatment of oncological and nononcological 

diseases. So far, clinical experience has shown type 1 

hypersensitivity reactions [7], which in rare cases result in severe 

side effects. Due to the mechanism of action, vesicant behaviour 

is highly unlikely, classifying them as low grade irritants. 

However, new humanised monoclonal antibodies, e.g. ipilimumab, 

brentuximab vedotin, emerge and for each individual compound 

the toxicity potential has to be evaluated again. 

Conclusion 

In summary, extravasation remains a dreaded complication of cytotoxic 

chemotherapy, at least for the next decade. Healthcare professionals 

engaged in extravasation management have to be aware of 

uncertainties and a possible lack of data regarding tissue toxicity of 

new compounds. This lack of knowledge should be addressed by an 

interdisciplinary ‘Extravasation Task Force’ engaging in the regular 

assessment of compounds, screening of literature, management of 

extravasation and their sequelae, adequate documentation, and publishing 

relevant information for the concerned scientific community. 

Authors 

Ursula Pluschnig, MD 

Professor Robert M Mader, DSc 

Clinical Division of Oncology 

Department of Medicine I 

Medical University of Vienna 

18-20 Währinger Gürtel 

AT-1090 Vienna, Austria 

robert.mader@meduniwien.ac.at 

Shahla Farokhnia, aHPh 

Gunar Stemer, aHPh 

Pharmacy Department 

University Clinics 

Vienna General Hospital 

AT-1090 Vienna, Austria 

References 

References can be found on page 17. 


19

Introduction 

DNA damage induced by endogenous and 

exogenous stimuli is a common event in 

every cell and its repair is routine because (as 

it is mandatory for cellular survival) efficient 

repair represents a strong survival advantage. 

The first report on DNA repair currently listed 

in MEDLINE dates from 1962 and 

describes the repair of UV-induced lesions. 

The knowledge that cells can recover from 

UV irradiation is even 30 years older than 

that. As there are a variety of different DNA 

lesions, cells have developed a matching variety of repair 

mechanisms some of which are interlinked and can serve as a 

backup for others if those happen to be ‘out of order’. Most of 

these mechanisms were discovered in the 1960s and 1970s [1]. 

Classical DNA-targeting anticancer agents are just another 

source of DNA damage causing more lesions than usual during 

chemotherapy. Naturally, tumour and normal cells alike 

will attempt to repair the damage. Supposing that DNA repair 

enables cells to revert to their original state, repair in normal 

(stem) cells is a good thing because it reduces side effects, 

whereas in tumour cells it is unfavourable because it may help 

the cell to survive, which decreases the clinical response. 

However, there is increasing evidence that cells surviving 

DNA damage due to DNA repair do not necessarily maintain 

their genomic integrity, but instead sustain non-lethal mutations. 

If such a mutation conveys a growth advantage over 

other cells, it may give rise to a secondary tumour or to secondary 

resistance of the primary tumour. 

DNA repair pathways 

DNA damage affects the bases, or the ‘backbone’ of DNA. 

Damage to the bases is repaired either directly by O6-methylguanine-DNA-methyltransferase 

(MGMT), mismatch repair 

(MMR), base excision repair (BER) or nucleotide excision 

repair (NER). A damaged backbone is equivalent to a DNA 

single or double strand break and is repaired by homologous 

recombination (HR) or non-homologous end-joining (NHEJ). 

For a recent review, see Pallis et al. [2]. 

The smallest alkyl residues, such as methyl and ethyl, are 

removed from the O6 position of guanine by MGMT which is 

also known as O6-alkylguanine DNA alkyltransferase (AGT). 

The modified guanine is directly reverted to its normal state, 

without the need to create and then fill a gap as with all other 



DNA repair in cancer therapy: beneficial or 

harmful 

A lot of research is being performed on the modulation of DNA repair and its exploitation as a therapeutic principle 

to enhance the effects of chemotherapy. This paper outlines chemotherapy-induced DNA damage, its 

repair, consequences and the current state of DNA repair inhibitor development. 

Professor Dorothee C Dartsch 

PhD 

forms of DNA repair. Anticancer agents, such as 

temozolomide, pro- and dacarbazine, and 

nitrosoureas transfer small alkyl residues and may 

be more effective in the absence of MGMT. 

Bases modified by larger alkyl residues or oxidation 

are repaired by BER. The first step is the 

removal of the damaged base by a glycosylase, 

which leaves an intact backbone with an abasic 

site. Secondly, an apurinic or apyramidinic 

endonuclease cleaves the backbone and generates 

a strand break which is recognised by 

PARP. PARP enables binding of subsequent repair proteins 

such as polymerases and ligases. Synthesis of DNA along the 

intact strand is accomplished either by polymerase β‚ (can also 

be substituted by polymerase λ if only one base is replaced, or 

polymerases ε or δ that replace 2–13 bases. The overhanging 

flap of replaced DNA is removed by FEN1 (Rad27) before the 

XRCC1/ligase III complex joins the newly synthesised patch 

with the old strand. 

If the chemical modification is even bigger, e.g. a bulky adduct 

or a thymidine dimer, the damage is repaired by NER. In 

regions of the genome that are not actively transcribed, the heterodimer 

of xeroderma pigmentosum (XP) protein C and 

hHR23B is required for damage recognition (global genome 

repair). Where active transcription occurs, transcription-coupled 

repair is not necessary to induce the next steps which are 

similar in both regions. The transcription factor IIH, replication 

protein (RPA) and a set of XP proteins (A, G, B, D, G, and 

F) cooperate to separate the two DNA strands at the damaged 

site, to stabilise the opening, and to excise 27–29 bases around 

the modified one. Subsequently, like in BER, polymerases ε or 

δ fill the gap and ligase III and/or ligase I join the strands. 

Some forms of DNA damage, if unrepaired, can give rise to 

base mismatches and subsequent insertions and deletions during 

DNA replication. These are reverted by the MMR pathway. 

Recognition is accomplished by the protein MLH1 in varying 

heterodimeric combinations. The newly synthesised strand 

(identifiable by the lack of methylation) is incised and 

unwound by helicase. DNA exonuclease I excises the region 

around the mismatch, DNA polymerase δ fills the gap within 

the new strand and DNA ligase I seals the backbone. 

The DNA double strand break is considered the most hazardous 

lesion because just one of them can cause cell death if 


21

it persists into mitosis, or genomic rearrangements if misrepaired. 

Two pathways have evolved that can accomplish 

repair of double strand breaks: HR and NHEJ. The pathway 

choice depends on different factors, e.g. cell type and cell 

cycle phase. In HR, recognition proteins named ATM and ATR 

recruit the ternary ‘MRN-complex’ that trims the 5’-ends at the 

break. This process is carried on by other enzymes and RPA 

binds to, and shelters, the generated single strand. In order to proceed 

with the repair, BRCA proteins 1 and 2 are needed to 

replace RPA with Rad 51. Binding of Rad 51 and/or XRCC 2 and 

3 proteins leads to alignment of the 

broken with a homologous intact 

strand. The latter serves as a template 

to re-synthesise the broken strand. 

HR also serves to repair interstrand 

crosslinks and lesions generated at 

stalled replication forks. NHEJ 

requires damage recognition by Ku 

70 and 80 proteins that bind to the 

ends of a break. They attract DNA- 

PKcs, an endonuclease that trims the 

ends of the broken strands and 

recruits polymerases λ and μ as well 

as DNA ligase IV that serve to fill the 

gaps and reseal the DNA backbones. 

An alternative form of NHEJ relies 

on PARP and the MRN complex to 

accomplish a limited resection of 

DNA ends at microhomology 

regions. Repair work is finished by 

the XRCC 1/ligase III complex. Thus, the alternative NHEJ pathway 

shares some key players with BER. 

Mutations in genes coding for DNA damage response-associated 

proteins are well known to cause severe disorders like 

ataxia telangiectasia, xeroderma pigmentosum, hereditary 

non-polyposis colorectal carcinoma, Bloom’s syndrome, 

BRCA-associated breast and ovarian cancers, and Fanconi 

anaemia. 

Chromosomal rearrangements and secondary 

malignancies 

Important knowledge about the long-term effects of anticancer 

chemotherapy comes from studies such as the British 

Childhood Cancer Survivor Study and the Childhood Cancer 

Survivor Study performed in the US and Canada. The first has 

followed, and is still following, a cohort of 17,981 five-year 

survivors of childhood cancer diagnosed with cancer at 

younger than 15 years between 1940 and 1991 in Great Britain 

(for the most recent publication see [3]). The second is a follow-up 

of 14,358 similar patients diagnosed between 1970 and 

1986 in the US and Canada (for the most recent publication see 

[4]). Of the childhood cancer survivors within these two studies, 

7.4% in the British and 9.6% in the American study had a 

diagnosis of a secondary neoplasm, which implies a cancer 

risk about four times higher than in the average, non-childhood 


cancer population after a median follow-up time of 24.3 and 

23.0 years from diagnosis, respectively. The most common 

secondary tumour entities (in descending order) were central 

nervous system (CNS) tumours (mainly gliomas), non-malignant 

skin cancer, gastrointestinal, genito-urinary, breast, and 

bone cancers in the British study and non-malignant skin cancer, 

breast, thyroid, CNS cancer, sarcoma, bone cancer and 

leukaemia in the American study [5]. Moreover, data from 

those patients who survive the first have a very high risk of 

developing further, secondary neoplasms. Among the British 

cancer survivors with a secondary 

neoplasm, most had been treated for 

the primary tumour with alkylants or 

anthracyclines, some with epipodophyllotoxins 

or platinum agents, and 

sometimes as combined radiochemotherapy. 

The distribution of primary 

anticancer therapies was similar in the 

American study, as can be deduced 

from the freely accessible study data 

(ccss.stjude.org). 

Other studies have revealed that secondary 

malignancies are characterised 

by distinct genetic rearrangements. 

One example is the study from 

Aguilera et al. who reported that, of 22 

children with therapy-related myelodysplastic 

syndrome/acute myeloid 

leukaemia, none had normal cytogenetics 

[6]. The most frequent alteration was a del(7) genotype 

(all of these patients had received prior therapy with alkylating 

agents) and a t(9;11) genotype (all patients had received etoposide). 

On the other hand, patients treated with alkylating agents 

frequently show a set of unbalanced genetic aberrations: the loss 

of the whole chromosomes 5 and/or 7 (-5/-7 genotype) or the 

gain of a whole chromosome 8 (+8 genotype) [7]. Thus, one 

might suspect that mutagenic anticancer agents leave a ‘fingerprint’ 

of typical genetic alterations. 

But how can there be characteristic translocations after the 

non-specific DNA damage inflicted by cytostatic compounds? 

To date, there are only vague hypotheses to explain 

this: the majority of random rearrangements may involve 

essential genes and, therefore, be lethal, which means that we 

do not see tumours with such rearrangements. Some agents 

have, if not a specific, then at least, a preferential site to 

cause damage, like the cleavage sites of topoisomerase II. 

The nuclear architecture may play a role in that it determines 

the proximity of certain chromosome bands and co-localisation 

with chromatin structural elements, e.g. topoisomerase 

II, scaffold attachment regions, regions of chromatin that are 

unprotected by histones and thus accessible for the transcription 

machinery and other enzymes working on DNA. Finally, 

an NHEJ signature has been found for all translocations 

known so far that consists of small deletions and duplications 


in each breakpoint, micro-homologies and non-template 

insertions [8]. 

DNA repair inhibition as a therapeutic principle 

It is probably too simplistic to assume that DNA repair guarantees 

cellular survival, as we and others were able to show 

that (at least in vitro) cells still die despite DNA repair [9-11]. 

Nevertheless, more and more studies suggest that it may be 

worthwhile to consider the effectiveness of the different repair 

pathways in order to guide the choice of the anticancer agent. 

For example, it has been shown that patients with a silent 

MGMT pathway benefit more from temozolomide, those with 

a low ERCC 1 level (NER pathway) from cisplatin, and those 

with an MMR defect from irinotecan, as opposed to patients 

with functioning repair pathways [12]. It is only a stone’s 

throw from this recognition to the idea that DNA repair might 

be systematically modulated in order to improve the effectiveness 

of chemotherapy. 

Inhibition of DNA repair, concomitant with a DNA-targeting 

chemotherapy is a compelling concept, not least because it 

may even possess some tumour specificity. Many tumours are 

characterised by abnormal DNA repair pathways. Thus, if 

there are two pathways A and B for a given DNA lesion and a 

tumour cell has a loss-of-function mutation for pathway A, it 

will be very vulnerable to DNA damage in the presence of an 

inhibitor of DNA repair pathway B, in contrast to a normal cell 

with two functioning repair pathways. This concept is called 

‘synthetic lethality’, and it is currently exploited mainly in 

BRCA 1/2 defective tumours. For a recent review see [13]. 

This defect occurs frequently in hereditary forms of breast and 

ovarian carcinoma, but also in some sporadic tumours, such as 

triple negative (i.e. estrogen receptor (ER), progesterone receptor 

(PR) and HER2 negative) breast cancer. Cells with a BRCA 

1/2 defect are over-reliant on PARP to initiate repair at double 

strand breaks generated by stalled replication forks. Inhibition 

of PARP in these cells has been shown to augment the effect of 

anticancer agents. These findings have prompted researchers 

and companies to further develop DNA repair inhibitors. 

The group of DNA repair inhibitors that is furthest along the 

road towards the market are inhibitors of a repair enzyme 

called poly(ADP-ribose) polymerase, PARP. The three early 

ones are iniparib, olaparib, and veliparib, which are now in 

phase III clinical studies. The PARP inhibitors tested so far 

have shown fair tolerability alone and in combination with 

chemotherapy. However, initial euphoria about the new and 

promising target has been followed by some disappointment 

concerning iniparib because a phase III trial with more than 

500 patients with triple negative breast cancer did not match 

the hopes kindled by earlier studies [14]. This does not, however, 

eliminate the class of PARP and other DNA repair 

inhibitors from the list of promising, new biological response 

modifiers. For one thing, iniparib is probably the weakest of 

the inhibitors, for another, it may still be effective in specific 

subsets of patients with breast cancer and/or patients with 

other tumours that were not adequately represented in the 

study. Furthermore, PARP is not the only interesting target 

among the DNA repair proteins. Research is currently addressing 

other proteins like MGMT, the CHK1 and 2, ATM and 

ATR kinases, Rad 51, and probably many more. 

A very relevant question will be the long-term safety of treatment 

with any DNA repair inhibitor. Naturally, this is a completely 

black box at the moment, and it will take many years to 

find the answers, as we know from long-term studies with 

classical antineoplastic agents. 

Author 

Professor Dorothee C Dartsch, PhD 

Professor of Clinical Pharmacy 

Institute of Pharmacy 

University of Hamburg 

45 Bundesstrasse 

DE-20146 Hamburg, Germany 

References 

1. Ljungman DG, et al. The DNA damage response: repair or despair? 

Environ Mol Mutagen. 2010;51:879-89. 

2. Pallis AG, et al. DNA repair pathways and their implication in cancer 

treatment. Cancer Metastasis Rev. 2010;29:677-85. 

3. Reulen RC. Long-term risks of subsequent primary neoplasms among 

survivors of childhood cancer. JAMA. 2011;305(22):2311-9. 

4. Armstrong GT, et al. Occurrence of multiple subsequent neoplasms in 

long-term survivors of childhood cancer: a report from the childhood 

cancer survivor study. J Clin Oncol. 29:3056-64. 

5. Meadows AT, et al. Second neoplasms in survivors of childhood cancer: 

findings from the childhood cancer survivor study cohort. J Clin 

Oncol. 2009;27:2356-62. 

6. Aguilera DG, et al. Pediatric therapy-related myelodysplastic syndrome/acute 

myeloid leukemia: the MD Anderson Cancer Center 

Experience. J Pediatr Hematol Oncol. 2009;31(11):803-11. 

7. Pedersen-Bjergaard, et al. Genetics of therapy-related myelodysplasia 

and acute myeloid leukemia. Leukemia. 2008;22:240-8. 

8. Schiavetti A, et al. Two secondary leukemias among 15 children 

given oral etoposide. Med Pediatr Oncol. 2001;37(2):148-9. 

9. Dartsch DC, et al. Repair of idarubicin-induced DNA damage: a 

cause of resistance? DNA Repair. 2007;6(11):1618-28. 

10. Schonn I, et al. Cellular responses to etoposide: cell death despite cell 

cycle arrest and repair of DNA damage. Apoptosis. 2010 Feb;15(2): 

162-72. 

11. Schonn I, et al. Ku70 and Rad51 vary in their importance for the 

repair of doxorubicin- versus etoposide-induced DNA damage. 

Apoptosis. 2011;16:359-69. 

12. Martin SA, et al. Genomic instability and the selection of treatments 

for cancer. J Pathol. 2010; 220(2):281-9. 

13. Shaheen M, et al. Synthetic lethality: exploiting the addiction of cancer 

to DNA repair. Blood. 2011:117(23):6074-82. 

14. Sanofi-aventis reports top-line results from phase III study with BSI- 

201 in metastatic triple-negative breast cancer [press release]. Sanofiaventis; 

2011 Jan 27. [cited 2011 October 21]. Available from: 

http://en.sanofi.com/Images/13666_20110127_BSI_en.pdf 


23

Introduction 

Myelodysplastic syndromes (MDS) are a heterogeneous group of 

myeloid haematologic disorders characterised by aberrant, clonal 

haematopoietic stem cells producing abnormal red blood cells, 

platelets, and neutrophils. These abnormal cells never fully mature 

and lead to cytopenias with patient sequelae of severe anaemia as 

well as fatal bleeding and infections. There is also the risk of transformation 

to acute myeloid leukaemia in MDS. Myelodysplastic 

syndromes is a disease of the elderly. Thus, as people’s lifespan has 

increased, the incidence and prevalence of MDS has risen over the 

last several decades. In Europe and North America, the median age 

of MDS patients at presentation is 76 years. Moreover, the incidence 

of MDS increases with age with the annual incidence rising from 15 

to 50 cases per 100,000/year in those aged 70 years and older [1]. 

Azacitidine (Vidaza®, Celgene Corporation, Summit, NJ, USA) is 

a cytidine nucleoside analogue and inhibitor of DNA methyltransferase 

[2-3], approved in the EU for treatment of higher-risk MDS, 

chronic myelomonocytic leukaemia (CMML, 10–29% marrow 

blasts without myeloproliferative disorder), and WHO-defined acute 

myeloid leukaemia with 20% to 30% blasts and multi-lineage dysplasia. 

Azacitidine has demonstrated the ability to prolong overall 

survival in patients with higher-risk MDS compared with conventional 

care [4]. 

Azacitidine is rapidly degraded in water by hydrolysis [2-3]. Thus, 

per current EU Marketing Authorisation, azacitidine is to be reconstituted 

with sterile water for injection (WFI) to form a suspension 

and then administered within 45 minutes if stored at 25ºC. After 

reconstitution with sterile WFI, azacitidine suspension may be 

refrigerated (2–8ºC) for up to 8 hours. Reconstituted under these 



® 

Cold water reconstitution of Vidaza ® with 

subsequent refrigerated storage prolongs 

drug stability 

Anthony Tutino1 , RPh; Mei Lai1,2 , PhD 

Abstract 

Study Objectives: This study assessed whether the stability of azacitidine suspension can be prolonged when reconstituted with 

refrigerated water for injection followed by storage under refrigerated conditions. 

Methods: Two lots of azacitidine (Vidaza) were reconstituted with refrigerated (2–8ºC) water for injection to form a suspension 

and immediately stored refrigerated (2–8ºC). After storage for 16, 18, 20, or 22 hours, azacitidine suspension was then placed at 

a constant 25ºC for 30 minutes then tested for potency, redispersibility time, and suspension appearance. Sterility testing was 

performed at the end of the study. Stability of azacitidine was defined as maintaining > 90% potency. 

Results: Azacitidine reconstituted with cold water (2–8ºC) followed by refrigerated storage (2–8ºC) and 30 minutes equilibration 

to 25ºC remained stable from baseline to 22 hours with a maximum loss of potency of 2.7% for each of the two lots of drug 

evaluated. At the 16, 18, 20, and 22 hour study time points and 30 minutes equilibration to 25ºC, redispersion time was 0.3 minutes 

with the appearance of fine white particles in suspension. All reconstituted vials stored refrigerated (2–8ºC) passed sterility 

testing at the end of study. Reconstitution of azacitidine with cold water for injection together with subsequent refrigerated storage 

is associated with a threefold prolongation in the stability time of the drug from 8 to 22 hours. 

Conclusion: This substantial increase in the time of azacitidine maintaining > 90% potency allows for prolonged in-use time that 

may provide for more convenience for pharmacists. 

Keywords: Azacitidine, cold water, reconstitution, stability, Vidaza 

conditions and times, azacitidine has been shown to remain stable (> 

90% potency). However, recent evidence suggests that the drug 

degradation of azacitidine may be slowed with a decrease in temperature 

of the WFI used for reconstitution. The purpose of this study 

was to assess whether reconstituting azacitidine with refrigerated 

WFI (2–8ºC) followed by refrigerated storage at 2–8ºC would prolong 

the drug stability time of azacitidine. 

Analytical methods and stability testing 

The potency of azacitidine was determined by quantitating the sample 

against an external standard utilizing reverse phase chromatography 

with UV detection. This method has been fully validated in 

accordance with ICH Guidance Q2 (R1) [5]. The determination of 

suspension appearance for redispersibility time was performed visually, 

in accordance with ICH guidelines [6]. All of the analytical 

methods have been registered and accepted by the EMA for the testing 

of azacitidine. 

Stability testing of azacitidine was performed by utilising validated 

regulatory accepted analytical methods in accordance with ICH 

guidelines [7]. These studies have been conducted at conditions 

which encompass long-term, intermediate and accelerated storage of 

the drug product over a period of time. The results of these stability 

studies on azacitidine have demonstrated product stability and have 

been acknowledged by the EMA. 

Materials and methods 

Two lots of sterile commercial scale azacitidine drug product, 

each nearing the end of their expiry period of 48 months, were 

used for the study. Each lot of drug product was prepared as a 

homogeneous mixture of lyophilized powder and placed in 


Table 1: Averaged* Azacitidine assay† Stability‡ after cold WFI reconstitution and refrigerated storage (2–8°C) from 

baseline (0 hours) to 22 hours 

Lot 1 

Baseline Average % 16 hours Average % 18 hours Average % 20 hours Average % 22 hours Average % 

for 3 vials* assay at BL for 3 vials* assay at 16 for 3 assay at for 3 assay at for 3 assay at 

hours vials* 18 hours vials* 20 hours vials* 22 hours 

Assay 95.3% 95.5% 93.7% 93.9% 94.2% 93.6% 91.6% 92.5% 92.5% 92.8% 

94.6% 94.3% 93.2% 93.0% 92.9% 

96.7% 93.7% 93.6% 92.9% 93.0% 

% loss of – 1.6% 1.9% 3.0% 2.7% 

assay from 

BL 

Lot 2 

Assay 95.2% 95.2% 94.6% 93.7% 93.6% 92.7% 92.8% 92.9% 93.7% 92.5% 

94.5% 93.2% 93.3% 92.6% 91.9% 

95.9% 93.3% 91.1% 93.4% 91.9% 

% loss of – 1.5% 2.5% 2.3% 2.7% 

assay from 

BL 

*Each averaged per cent comes from 3 vials of product; †% per EU Marketing Authorisation; ‡Stability of Vidaza based on maintenance of > 90% potency. 

WFI, water for injection. 

labelled vials in preparation for reconstitution. Vials from each 

lot of azacitidine drug product were then reconstituted with 4 

mL of refrigerated (2–8ºC) WFI and immediately placed in 

refrigerated storage (2–8ºC). After refrigerated storage for 16, 18, 

20, and 22 hours, reconstituted vials of azacitidine were removed 

from refrigeration and placed at 25ºC for 30 minutes. 

Equilibration time to 25ºC for refrigerated azacitidine suspension 

has been previously determined to be 30 minutes per EU 

Marketing Authorisation. After 16, 18, 20, and 22 hours of refrigerated 

storage and 30 minutes equilibration to 25ºC, the reconstituted 

vials were shaken vigorously and tested for potency, 

redispersibility time, and appearance of the suspension. Stability 

of azacitidine was defined as maintaining > 90% potency. 

Sterility of the refrigerated drug product was assessed for reconstituted 

vials stored at 2–8ºC at end of study. 

Results 

After cold water (2–8ºC) reconstitution and refrigerated storage 

(2–8ºC) followed by 30 minutes equilibration to 25ºC, azacitidine 

remained stable from baseline to 22 hours with a maximum loss of 

potency of 2.7% for each of the 2 lots of drug product evaluated, see 

Table 1. At the 16, 18, 20, and 22 hour study time points and 30 

minutes equilibration to 25ºC, redispersion time was 0.3 minutes 

with the appearance of fine white particles in suspension and the 

absence of clumps. All reconstituted vials stored refrigerated (2–8ºC) 

passed sterility testing at end of study. 

Discussion 

Because azacitidine readily degrades in water after reconstitution, 

the drug—per the EU Marketing Authorisation—must be administered 

within 45 minutes when stored at 25ºC and within 8 hours 

under refrigerated conditions to assure maintenance of potency of 

> 90%. The results of this trial, however, show that the stability 

(> 90% potency) and usage time of reconstituted azacitidine can be 

prolonged nearly threefold from 8 hours to 22 hours using cold water 

(2–8ºC) reconstitution followed by refrigerated (2–8ºC) storage. 

This reconstitution procedure showed no effects on redispersibility, 

appearance, or sterility after the prolonged refrigerated storage time. 

These findings have important implications for providing expanded 

usage time with azacitidine for pharmacists and other caregivers. 

Conclusion 

Reconstitution using cold WFI followed by refrigerated storage is 

associated with a threefold prolongation in the stability time of azacitidine 

(8 to 22 hours). This substantial increase in the time of azacitidine 

maintaining > 90% potency allows for prolonged in-use time 

that may provide for more convenience for pharmacists. 

Acknowledgements 

The authors wish to acknowledge the assistance of Acceleration 

Laboratory Services, Inc, 2634 NE Hagan Road, Lee’s Summit, 

MO 64064, USA, in the conduct of this study and the writing assistance 

of Mr Neil Malone, MA, of Celgene Corporation, in the development 

of this manuscript. 


Anthony Tutino 1 , RPh 

1 Celgene Corporation 

Pharmaceutical Development 

110 Allen Rd 

Basking Ridge, NJ 07938, USA 

Tel: +1 908 8604071 

Fax: +1 908 8604079 

atutino@celgene.com 

Co-author 

Mei Lai 1,2 , PhD 

2 Clovis Oncology, Pharmaceutical 

Development, Boulder, CO, USA 

References 



25



A practical approach to oral tumour therapy 

Oral anti-tumour drugs present many challenges for medical staff, pharmacists, and patients [1]. A recent German 

Society for Oncological Pharmacy (DGOP) initiative sought to address some of the more urgent questions in this 

complex field [2]. This article summarises the collaborative thoughts of a haemato-oncologist and a pharmacist. 

The problem 

Oral anti-tumour drugs are commonly considered 

to be less aggressive, less toxic, and less 

problematic than their IV counterparts. 

However, despite the long-term availability of 

some of these agents, there is no recent guidance 

regarding the administration of these drugs. In 

order to achieve optimal patient outcomes, it is 

vital that information is constantly updated. This 

helps to ensure that well established compounds 

such as busulfan or cyclophosphamid, and fairly 

new targeted therapies such as imatinib and everolimus, continue 

to be used optimally. Some of the most commonly available oral 

tumour therapies are listed in Table 1. 

This article focuses on small (low) molecular (weight) kinase 

inhibitors (SMKIs), considered by many experts to be the ‘rising 

stars’of personalised targeted therapy. SMKIs are considered to be 

highly selective against tumour cells, but they can also have 

severe, sometimes life-threatening side effects. Their toxicities 

affect most organs, and include carcinogenic, mutagenic, and toxic 

to reproduction effects. These toxicities result from inhibiting not 

only tumour-dependent kinases in the tumour cells, but also the 

normal variant counterparts in healthy cells, exactly as classical 

chemotherapy affects both the tumour and host organism. 

Compliance 

Oral (chemo-) therapy relies heavily on patient compliance. 

Physicians and nurses must therefore work together to explain the 

therapy to the patient, and counter any individual fears and side 

Jürgen Barth 

Table 1: Classes and INN names of oral anti-tumour therapeutics 

Alkylating agents Antimetabolites Podophyllotoxine IMIDs SMKI 

derivatives 

Busulfan Capecitabine Etoposide Lenalidomide Dasatinib 

Chlorambucil Fludarabinphosphate Topoisomerase I Pomalidomide* Erlotinib 

inhibitor 

Cyclophosphamide Methotrexate Topotecan Thalidomide Everolimus 

Estramustine Mercaptopurine Topoisomerase II Gefitinib 

inhibitor 

Lomustine S 1 Idarubicin Imatinib 

Melphalan Tegafur-uracil Vinca-alkaloides Lapatinib 

Procarbazine Tioguanine Vinorelbine Nilotinib 

Temozolomide Other Pazopanib 

Treosulfan Hydroxycarbamid Sorafenib 

Trofosfamide Mitotane Sunitinib 

Hormone/anti- Vandetanib 

hormones 

IMIDs: immune modulatory drugs; *Pomalidomide not yet approved. 

effects. Oral therapy may lead to an increased 

quality of life and greater self-management, but if 

this type of therapy is mismanaged, it can evoke 

serious side effects and become burdensome. 

Food 

The bioavailabilities of oral cytostatics vary extensively, 

depending on the timing of concomitant 

food intake. The effect of fat or other food components 

may result in over or underdosing, depending 

on the exact drug administered. Table 2 provides 

an overview of recommended oral SMKI administrative timing 

in relation to food intake. 

Knowledge 

Patients need to know the advantages and disadvantages of 

their therapy, their exact dosing requirements, and why they 

should not discontinue therapy. To achieve these objectives, 

doctors and pharmacists must work together, the therapy must 

be practical enough to fit in with the patient’s daily routine, 

and the patient must be informed of the exact circumstances 

when he/she should contact his/her physician. During the 

patient consultation, however time-consuming or demanding it 

may turn out to be, it is essential to ensure that the patient 

agrees to the therapy and that the information provided is not 

intimidating, overwhelming, or complicated. 

Interactions 

Concomitant intake of medicines with food and/or other drugs 

may result in unwanted interactions between the cytochrome P450 

superfamily of metabolic enzymes. 

However, these interactions 

only become important if they 

result in a clinically significant 

effect, e.g. an inhibition of degradation 

that causes a 2- to 5-fold 

difference in predicted plasma 

levels. Like approximately 50% 

of therapeutic entities, SMKIs are 

metabolised by CYP3A4. When 

two molecules are simultaneously 

metabolised by CYP3A4, it is 

difficult to predict which one will 

take precedence. As a practical 

approach, all medicines and supportive 

agents such as vitamin 

or mineral tablets must be 

reported, the patient must be 

informed of any potential inter- 


actions, and if applicable he/she must refrain from their concomitant 

medication. 

Table 2: Recommended SMKI administration in relation 

to food intake 

To be taken with 

food 

To be taken 

without food 

No matter 

Imatinib Erlotinib 

Everolimus 

Lapatinib 

Nilotinib 

Pazopanib 

Sorafenib 

Dasatinib 

Gefitinib 

Sunitinib 

Vandetanib 

Side effects and toxicity management 

SMKIs that target the epidermal growth factor receptor 

(EGFR) and the anti-EGFR-monoclonal antibodies, also act 

against the EGFR in normal skin. This can evoke dermatotoxicities 

such as inflammation and acne-like efflorescence, without 

the bacterial infection. Firstly, the skin changes in a way 

similar to acne, then it becomes dry, and finally it is rendered 

very sensitive and dry. There are many recommendations 

available for reversing all of these three phases [3-5]. 

There is some evidence to suggest that RAF-kinase inhibitors 

may evoke secondary malignancies such as carcinoma of the 

epithelium [6]. As a consequence, pharmacists, physicians, 

and nurses should monitor closely any changes in the patient’s 

skin. 

SMKI inhibition can also adversely affect several healthy 

kinase variants in the heart [7]. The fusion protein BCR/Abl is 

the molecular driver of chronic myeloid leukaemia, and 

because dasatinib, imatinib and nilotinib not only inhibit 

BCR/Abl but also the unmutated form of the Abelson-kinase 

that is essential for cardiomyocyte survival, heart function can 

become diminished. Off-target cardiotoxicity has also been 

reported with other SMKIs, including RSK, RAF, and HER2. 

As a consequence, heart function should be monitored for the 

duration of SMKI therapy. This includes the monitoring of QT 

changes, a sign of arrhythmia. 

Other organs that can be affected by SMKI toxicity are the thyroid 

gland (sunitinib, pazopanib) and the liver [8]. Blood pressure is 

influenced by all anti-angiogenic agents, e.g. vascular endothelial 

growth factor inhibitors, and routine blood pressure monitoring is 

therefore necessary. Class effects include hypertension and venous 

thrombosis. 

Gastrointestinal toxicity 

All known ATP mimetics cause (sometimes dose-limiting) diarrhoea, 

and some degree of nausea and vomiting. Many patients 

seem uneasy talking about diarrhoea. Initially, patients need to 

understand the definition of diarrhoea. Grades of diarrhoea are 

clearly defined in the Common Terminology Criteria for 

Adverse Events version 4.0, 28 May 2009, by the number of 

stools per day, and if applicable, ostomy output. Intervention 

can include the use of loperamide. Ciprofloxazin use is mandatory 

if diarrhoea persists for more than 48 hours. Octreotid can be 

regarded as rescue medication if symptoms continue to persist. 

Conclusions 

• Close collaboration between the physician, nurse and pharmacist 

is essential for guiding the patient through oral chemotherapy. 

• Medical and pharmaceutical staff should be highly educated 

about oral anti-tumour therapies. 

• Prescriptions should always be dispensed on time. 

• Physicians and pharmacists should share patient information and 

ensure that it is as helpful as possible. 

• Oral tumour therapy is complex, and all healthcare stakeholders 

should work together. 

• Confidence and clarity are mandatory when advising patients 

about the importance of compliance. 

• All recommended supportive medications should be closely scrutinised, 

and should be chosen after careful consideration of the 

patient’s individual situation—an inability to do so may be counter-productive. 

Author 

Jürgen Barth 

Specialist in Clinical Pharmacy and Oncology Pharmacy 

Justus Liebig University 

Medizinische Klinik IV 

Universitätsklinik 

36 Klinikstrasse 

DE-35385 Giessen, Germany 

References 

1. Barth J. Kompetente Antworten auf scheinbar leichte Fragen. Onkologische 

Pharmazie. 2009;11(3):4-7. 

2. Deutsche Gesellschaft für Onkologische Pharmazie (DGOP). Orale 

Zytostatikatherapie — sicher und effektiv durch gemeinsame Beratung. 

Available from: www.dgop.org/anmeldung_kampagne.php 

3. Lacouture ME. Mechanisms of cutaneous toxicities to EGFR inhibitors. 

Nat Rev Cancer. 2006;(10):803-12. 

4. Potthoff KM, Hassel JC, Wollenberg A, et al. Therapie und Prophylaxe 

EGFR-Inhibitor-induzierter Hautreaktionen. Arzneimitteltherapie. 2010; 

28:191-8. 

5. Schimanski CC, et al. Cetuximab-induced skin exanthema: Improvement 

by a reactive skin therapy. Mol Med Report. 2010;3(5):789-93. 

6. Dubauskas Z, et al. Cutaneous squamous cell carcinoma and inflammation 

of actinic keratoses associated with sorafenib. Clin Genitourin Cancer. 

2009;7(1):20-3. 

7. Force T, Krause DS, Van Etten RA. Molecular mechanisms of cardiotoxicity 

of tyrosine kinase inhibition. Nat Rev Cancer. 2007;7(5):332-44. 

8. Loriot Y, et al. Drug insight: gastrointestinal and hepatic adverse effects of 

molecular-targeted agents in cancer therapy. Nat Clin Pract Oncol. 

2008;5(5):268-78. 


27



Setting up a pharmacist-led chemotherapy 

clinic: a practical guide 

In the UK, several pharmacist-led chemotherapy clinics have been reported. The increasing use of oral 

chemotherapy is revolutionising the way that chemotherapy services are provided. This article is a practical 

guide for oncology pharmacists who are considering setting up a chemotherapy clinic. 

Introduction 

In the UK, pharmacists and nurses have been 

able to train as prescribers since 2003. 

Initially, this was in partnership with a doctor 

(called supplementary prescribing), but more 

recently, pharmacists have been able to prescribe 

independently. Under current legislation, 

trained pharmacists can prescribe the 

full range of licensed and unlicensed medicines, 

with the exception of controlled drugs 

such as opiates. 

The chemotherapy clinic at Airedale Hospital, West Yorkshire, 

UK, has been running since before these changes were introduced—a 

doctor was required to sign all the prescriptions 

which were prepared by the pharmacist. The introduction of 

pharmacist prescribing simplified the pathway and allowed 

development of new services. 

In the UK, several important national documents have highlighted 

the risks of chemotherapy treatment and advised services 

to look for innovative ways of working to ensure safer 

treatment for patients [1, 2]. The introduction of pharmacistled 

chemotherapy clinics is one way in which some services 

are doing this [3-5]. 

In addition, the introduction of consultant oncology pharmacists 

means that pharmacists are well placed to take on some 

of the roles more traditionally associated with medical oncologists 

[6, 7]. 

This article is a brief practical guide for oncology pharmacists 

who are considering setting up a chemotherapy clinic. 

The groundwork 

The first consideration should always be to think about 

whether a pharmacist-led clinic is required within the local 

service. There must be clear benefits for patients and for the 

service. It is vital that discussions take place between pharmacists, 

oncologists, nurses and managers. Some benefits of 

pharmacist-led clinics are shown in Table 1. 

It is useful to include patients in discussions about new services; 

they can give useful insights into what they want as users 

of the new service. When clinical and managerial support has 

been established, a robust business case is required. This 

details the costs involved in setting up the service to include 

Carl Booth, BPharm, MPhil, 

MRPharmS IP 

staff costs and facilities and also any income 

generated by the clinic. Think about what backfill 

may be required to cover the pharmacist’s 

other duties and who will cover the service in 

the event of holiday or sickness. 

If there are any similar clinics already running 

within the local area, arrange to visit them and 

speak to the staff who have already been 

through the process. Colleagues are usually 

willing to give you advice on where things went 

well or badly. 

A very important point is to audit the current service before 

you make any changes. This will give you some useful information 

to demonstrate the benefits of your new service at a 

later date. 

Setting up the new clinic 

It is important to identify the group of patients you will see in 

the clinic. In large centres this might be a specific group, such 

as colorectal cancer patients on capecitabine. In smaller centres 

it might be all capecitabine patients, or patients on oral 

chemotherapy treatment. Remember that you may not see 

many patients at first, but if the clinic is a success, the numbers 

will build up over time and you will need to plan ahead so that 

you are not over booking clinics, leading to delays for patients 

and stress for staff! 

Consider which staff need to be involved in the clinic. Will 

you be running it alone or in partnership with an oncology 

nurse or medical oncologist, and how will patients be referred 

to your clinic? 

Think about the facilities that will be required. There may be 

space in the outpatient clinic or on the chemotherapy day unit. 

Table 1: Benefits of pharmacist-led chemotherapy clinics 

Patient benefits: 

• direct access to a medicines expert 

• quicker access to medicines 

• shorter waiting times 

Service benefits: 

• reduced costs compared with medical oncology clinics 

• increased capacity of medical clinics 

• reduced workload on chemotherapy day units 

• improved team working and job satisfaction 

• compliance with national standards 


Ensure that you have access to IT services such as blood 

results or prescribing systems. 

It is essential that protocols are in place before you start to 

see patients in the clinics. This will ensure that you work 

within locally agreed boundaries, ensure the safety of 

patients and support the staff. You will need access to the 

patient record, which may be paper or electronic medical 

notes. In our chemotherapy consent clinic we have individual 

patient plans for each regimen and disease state. The 

medical oncologist signs the correct plan when the decision 

to start chemotherapy is made in the outpatient clinic and 

this acts as a referral to the pharmacy and nurse-led 

chemotherapy consent clinic and also as a treatment plan for 

prescribing chemotherapy. 

Check that you have authorisation to undertake clinical tests 

that you might need to order. If not, then request permission 

from your employing hospital or put systems in place to 

ensure that these tests are ordered in advance. In some cases 

you may require test results to be available on the day of the 

clinic in order to prescribe chemotherapy. It may be useful 

to get these done the day before to ensure that the patient is 

not waiting. 

Running the clinic 

Once the clinic details have been finalised and the clinic is 

ready to start, make sure that patients are clear about whom 

they will be seeing in the clinic. If patients are expecting to see 

their medical oncologist they may be concerned to see a pharmacist 

in the clinic. Agree the wording of clinic letters with the 

medical secretaries to make sure the location and timing of the 

clinics is clear. If you want patients to bring their medicines, or 

a list of medicines, then this request should be added to the 

clinic letter. 

An important point to consider is how you will access medical 

assistance if needed. If you see a patient in the clinic who 

becomes acutely unwell or who exhibits signs of illness that 

require medical assessment, how will this be arranged? It may 

be an informal arrangement with the medical oncologist or oncall 

physician to call if needed, or it may be that you run your 

clinic alongside an oncologist so that assistance is always on 

hand. 

Make sure that all your actions with the patient are documented 

in the medical record. You may need to be able to justify 

your actions at a later date. 

Reviewing the service 

Once you have your clinic up and running, it is not time to sit 

back and relax! Consider the first few clinics as a pilot, following 

which you may wish to make changes in how the clinic 

runs. Think about what went smoothly and what could have 

been done better. Did the clinics run to time and did you have 

access to everything you needed? 

Once the clinic is established as a long-term service then consider 

auditing to establish whether the proposed benefits to 

patients and to the service have been achieved. Compare your 

results with the baseline audit which you carried out before 

setting up the service. Consider undertaking a patient satisfaction 

survey. 

Outcomes should be presented locally, for example at clinical 

governance meetings. It is important to disseminate your 

results more widely at meetings and conferences. Positive outcomes 

from your new clinic will assist other pharmacists in 

making the case for their new clinic. 

Hopefully your new clinic will become a beacon of clinical 

oncology pharmacy practice. You can use it to train junior 

pharmacists and senior colleagues alike. Where patients have 

a choice about where they are treated it may also be used to 

attract patients to your oncology service. Finally, it may be 

used to attract and retain oncology pharmacists where they can 

use the clinic to develop their knowledge and skills in oncology 

working towards advanced levels of clinical practice. 

Author 

Carl Booth, BPharm, MPhil, MRPharmS IP 

Lead Pharmacist 

Cancer Services and Clinical Trials 

Airedale NHS Foundation Trust 


Airedale General Hospital 

Skipton Road, Steeton, Keighley 

West Yorkshire BD20 6TD, UK 

References 

1. Department of Health. Systemic anti-cancer chemotherapy, for better 

or worse? A report by the National Confidential Enquiry into Patient 

Outcome and Death. London: DH; 2008. 

2. Department of Health. Chemotherapy services in England: ensuring 

quality and safety. A report from the National Chemotherapy Advisory 

Group. London: DH; 2009. 

3. Booth CD, Dyminski P, Jeyasangar G. Chemotherapy Consent Clinic. 

Healthcare Pharmacy. Apr 2005;2(2):24-5. Available from: www.nelm. 

nhs.uk/en/NeLM-Area/Evidence/Medicines-Management/References/ 

2005 May/24/Chemotherapy-consent-clinic/ 

4. Donovan G, Evans S. Development of nurse/pharmacist-led clinic for 

the treatment of breast cancer. Adv Breast Cancer. 2005; November: 

47-9. 

5. Bowden EM, Horne N. 59 A joint non-medical prescribing clinic for 

the management of patients requiring tyrosine kinase inhibitors and 

chemotherapy treatments led by a lung cancer clinical nurse specialist 

and a Macmillan pharmacist. Lung Cancer. 71 (Suppl. 1), 2011, S20. 

doi:10.1016/S0169-5002(11)70059-9 

6. Department of Health. Guidance for the development of consultant 

pharmacist posts. London: DH, 2005. 

7. Kirk S. Diversity of a consultant oncology pharmacist’s role. British 

Journal of Clinical Pharmacy. 2010;(2):23-4. 


29

Update 


Clinical evaluation of lenograstim use in the 

Bank of Cyprus Oncology Centre 

The purpose of this observational study was to evaluate the effect of lenograstim (G-CSF) prophylaxis on febrile 

neutropenia incidence in chemotherapy-receiving patients with solid tumours. 

Introduction 

Febrile neutropenia 

Cytotoxic chemotherapy suppresses 

the haematopoietic system 

impairing host-protective mechanisms. 

Neutropenia, the most serious 

haematologic toxicity, can lead 

to febrile neutropenia (FN), which 

usually requires immediate hospitalisation 

and antibiotic treatment 

[1, 2]. The mean level of in-hospital 

mortality associated with 

Andri Kouroufexi 

MSc 

patients hospitalised with FN is 9.5%. This percentage rises above 

21% for patients with co-morbidities [3]. Chemotherapy dose 

reductions and dose delays, as a result of neutropenia and FN, can 

lead to reduced patient survival [4, 5]. 

The granulocyte-colony stimulating factors 

Granulocyte colony-stimulating factors (G-CSFs) stimulate the proliferation 

and survival of neutrophils and their precursors, thereby 

reducing the incidence and severity of neutropenic complications 

across a range of malignancies, and facilitating the delivery of fulldose 

chemotherapy [6]. Lenograstim is the glycosylated recombinant 

form of human G-CSF. Several randomised controlled trials 

have confirmed the efficacy and safety of these agents, and a metaanalysis 

involving chemotherapy-receiving adult cancer patients 

was recently performed [7]. All forms of G-CSF evoked significant 

reductions in FN risk in both solid tumour patients and those with 

non-Hodgkin’s lymphoma. Notably, a significant reduction in FN 

risk was observed across a broad range of baseline levels of risk 

ranging from 17 to 90%. A significant reduction in infection-related 

and early all-cause mortality was also demonstrated. These observations 

are consistent with that of a Cochrane meta-analysis of therapeutic 

CSF in patients hospitalised with FN following cancer 

chemotherapy [8]. The meta-analysis also confirmed the ability of 

these agents to sustain chemotherapy-relative dose intensity. 

Economic considerations 

Despite the ability of G-CSFs to reduce the risk of serious 

chemotherapy-related toxicities, many patients who receive 

myelosuppressive chemotherapy do not receive concomitant 

myeloid growth factors. While the decision to utilise a G-CSF in 

chemotherapy patients should be based primarily on clinical indications, 

the cost of these agents often raises economic considerations 

at the institutional and societal level. The direct costs of 

myeloid growth factors should be balanced against the reduction in 

costs of FN hospitalisation, the reduction in early infection-related 

mortality, and overall survival. It is anticipated that by identifying 

Stavroula Theophanous- 

Kitiri, MSc 

George Polykarpou 

MSc 

patients who are most at risk from 

these complications, i.e. those who 

are most likely to benefit from prophylactic 

myeloid growth factors, 

the risk of these serious complications 

could be reduced in an efficient 

and cost-effective manner. 

Clinical practice guidelines 

Clinical practice guidelines for the 

use of G-CSFs have been developed 

by various professional 

organisations, including the European Organisation for Research 

and Treatment of Cancer (EORTC) [9], the National 

Comprehensive Cancer Network [10], and the American Society 

of Clinical Oncology [11]. They agree that any patient with an FN 

risk greater than 20% should receive primary prophylaxis with 

G-CSF alongside each chemotherapy cycle. In some instances, the 

chemotherapy regimen itself carries an FN risk that exceeds this 

threshold. If the FN risk associated with the regimen is 10–20%, 

the physician should consider whether patient factors take the 

overall risk beyond 20%. If the chemotherapy regimen is considered 

to present an FN risk of less than 10%, primary prophylaxis 

with G-CSF should not be offered, unless the risk of serious FN 

complications is considered high. 

Patients and methods 

An evaluation of the use of lenograstim in actual practice as measured 

by the incidence of subsequent FN in patients with solid 

tumours who undergo chemotherapy would be useful for clinicians 

who are seeking to develop an evidence-based reimbursement 

policy for these drugs. 

Consequently, we conducted such a study in the Bank of Cyprus 

Oncology Centre, Nicosia, Cyprus. A total of 482 patients who 

received G-CSF between February 2008 and January 2010 were 

identified and selected from the pharmacy computer system Power 

Pro. Patient data and blood test results were retrospectively 

obtained from medical records and Mosaiq software, a standard 

data collection form was developed, and the following information 

was recorded: height, weight, date of birth, diagnosis, stage of disease, 

and details of prior or concomitant radiotherapy. Any delays 

in the administration of chemotherapy (with explanations) were 

recorded, as was the absolute neutrophil count at the time of delay, 

and details of whether the patient had experienced neutropenia 

during the cycle in question. When the dose of administered 

chemotherapy was less than optimal, the reason for the dose reduction 

and the relative percentage of the administered dose versus the 


31

planned dose were recorded. Use of G-CSF and antibiotics— 

reason, dose and frequency of administration, total number of 

doses—were also recorded. Results were recorded in Microsoft 

Excel and analysed using an SPSS database. 

Results 

Between February 2008 and January 2010, 1,791 patients admitted 

to the Centre received chemotherapy. Eight hundred and fortysix 

(47.2%) patients received lenograstim after myelosuppressive 

chemotherapy. Of these 846 lenograstim courses, 482 (57%) were 

included in the study, see Figure 1. 

Figure 1: Patients receiving lenograstim between February 

2008–January 2010 

Included in 

study 

482/846 (57%) 

patients 

G-CSF 

846/1,761 (47.2%) 

patients 

Lenograstim administration 

A total of 12,037 administrations of lenograstim were recorded in 

482 patients. The median number of injections administered per 

patient per chemotherapy cycle was 5 (range 1–10 injections). In 

most patients, administration was initiated either 48 hours (57% of 

cases) or 72 hours (36% of cases) post-chemotherapy. Overall, 

76.1% (367/482) of patients received prophylactic administration of 

lenograstim. The distribution of cancer types was 61.8% (298/482) 

breast, 12.4% (60/482) lung, 7.5% (36/482) lymphoma, 3.1% 

(15/482) head/neck, 2.7% (13/482) colorectal, 2.7% (13/482) sarcoma, 

2.5% (12/482) testicular, 2.5% (12/482) gynaecological, and 

4.8% (23/482) other, see Figure 2. The majority of recruited patients 

were female (75%), consistent with this tumour-type distribution. 

Figure 2: Patient diagnosis 

February 2008–January 2010 

1,761 patients 

Not included 

in study 

364/846 (43%) 

patients 

No G-CSF 

945/1,761 (52.8%) 

patients 

Breast 

Lung 

Lymphoma 

Head/Neck 

Colorectal 

Sarcoma 

Testis 

Gynaecological 

Other 

Incidence of FN 

Following primary prophylaxis with lenograstim, the incidence of 

FN varied between the different cancer types. The malignancies 

Update 

associated with the highest FN incidence were sarcoma and 

head/neck cancer [30.8% (4/13) and 26.7% (4/15), respectively]. 

Breast cancer was associated with the smallest FN incidence [5% 

(15/298)], see Figure 3. 

Figure 3: Incidence of FN after lenograstim administration 

Delivery of full-dose chemotherapy 

Ninety-seven per cent (468/482) of patients received full-dose 

chemotherapy as per protocol. Overall, nine courses of chemotherapy 

were delayed for ≥ 7 days in 9/482 (2%) patients, and 5/482 

(1%) patients required dose reduction ≥ 15% due to prolonged 

neutropenia, see Figure 4. 

Figure 4: Delivery of full dose chemotherapy 

Antibiotic therapy 

Ninety-six episodes of FN (82 patients) requiring hospitalisation 

occurred while patients were receiving prophylactic G-CSF. The 

mean duration of hospital stay was five days. Sarcoma and lung 

cancer patients required the longest period of hospitalisation (mean 

six days). The empiric antibiotic of choice was piperacillin/tazombactam 

+ gentamycin, as administered in 82.4% (79/96) patients. 

Ciprofloxacin 500 mg was administered in 73.6% (50/68) patients. 

Positive cultures were found only in seven patients (8.5%). Of the 

organisms isolated, 5/7 (71.4%) were gram-positive bacteria and 

2/7 (28.6%) were gram-negative bacteria. 

Adverse events 

Various adverse events were observed following primary prophylaxis 

with G-CSF. The most frequently reported adverse 

event was bone pain, which was recorded in 30.7% (148/482) 

of patients. This bone pain was mild to moderate in severity, 

and in most patients (83.8%), was successfully treated with 

paracetamol. 

32 European Journal of Oncology Pharmacy • Volume 5 • 2011 • Issues 3-4 www.ejop.eu 

FN incidence 

patients (%) 

Sarcoma 

Head/Neck 

Testis 

Cancer type 

Lung 

Lymphoma 

Breast 

Colorectal 

Gynaecological 

Complete chemotherapy 

Dose delay ≥ 7 days 

Dose reduction ≥ 15%

Assessment of risk for neutropenic complications according to 

EORTC guidelines 

According to EORTC guidelines for G-CSF administration, 19.6% 

(72/367) of our patients who received primary prophylaxis would 

be categorised in the low-risk FN category, 30.8% (113/367) 

would be categorised in the intermediate-risk category, and 49.6% 

(182/367) would be categorised in the high-risk category. Our lowrisk 

patients reported a smaller incidence of FN, but a higher incidence 

of neutropenic complications, suggesting that prophylactic 

administration of growth factors in these patients improved overall 

outcome. Numbers, however, were small, see Figure 5. 

Figure 5:Assessment of risk for neutropenic complications 

as per EORTC guidelines 

< 10% FN risk 

72/367 (19.6%) 

5/72 

(8.3%) 

4/72 

(5.6%) 

2/72 

(2.8%) 

Primary prophylaxis 

67/482 (76.1%) 

10–20% FN risk 

113/367 (30.8%) 

7/113 

(6.2%) 

2/113 

(1.8%) 

1/113 

(0.8%) 

Patients who received 

lenograstim 

482 

> 20% FN risk 

182/367 

17/182 

(9.3%) 

3/182 

(1.6%) 

4/182 

(2.2%) 

Secondary prophylaxis 

115/482 (23.9%) 

Febrile 

neutropenia 

Dose delay > 

7 days 

Dose reduction 

> 15% 

Conclusion 

The results of our study showed that almost half of the patients who 

received chemotherapy in the Centre also received lenograstim. 

More than half of these patients were women with breast cancer. 

Following lenograstim primary prophylaxis, almost all patients 

received full-dose chemotherapy without any modifications. 

Our results also showed that G-CSF may currently be misdirected 

toward low-risk patients, incurring unnecessary expense. 

According to guidelines, G-CSF treatment has limited cost-effectiveness 

in low-risk patients, in whom alternative management 

approaches are safe and inexpensive. Conversely, in extremely 

high-risk populations, it is unlikely that G-CSF therapy could 

decrease costs, since early hospital discharge is rarely feasible. 

Therefore, it is probably an intermediate-to-high-risk population 

that is most likely to benefit from G-CSF therapy, and thus, 

lenograstim should be used as part of the standard therapy in the 

management of FN patients with solid tumours meeting these risk 

criteria. 

It is evident that healthcare practitioners should improve G-CSF 

use in the hospital setting to facilitate cost-effective therapy. Our 

results have assessed many factors, which may lead to modifications 

in practice, new guideline recommendations and better outcomes 

in the Centre. Perhaps every cancer hospital should undertake 

their own assessment and produce their own guidelines for 

managing such patients. Further studies are warranted to determine 

the best efficacious and cost-effective G-CSF prophylactic options 

for patients at each level of risk. 


Andri Kouroufexi, MSc 

Clinical Pharmacist 

Makarios Hospital 

Nicosia, Cyprus 

Co-authors 

Stavroula Theophanous-Kitiri 1 , MSc 


Head of Pharmacy Department 

George Polykarpou 1 , MSc 


Yiola Markou, MD 

Medical Oncologist 

1 Bank of Cyprus Oncology Centre 

Strovolos, Cyprus 

Evangelia Papadimitriou, PhD 

Department of Pharmacy 

University of Patras, Greece 

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33

ANNOUNCEMENT 

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Cold water reconstitution of Vidaza® with subsequent refrigerated storage prolongs drug stability 


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/Q1A_R2_Guideline.pdf 




Hospital workers perceptions about nanotechnology 

Nagwa Ibrahim, PharmD, FAIHQ; Ali Al Zahrani, MD, FRCR; Ashraf Al Alwan, PhD 

Nanotechnology is the tiny world of controlling matter at the scale of one billionth of an atom. In the last 

few years, nanotechnology has catapulted from being the specialty of a few physicists and chemists to a 

worldwide scientific and industrial enterprise. 

Introduction 

The rapid development of nanotechnology and the growing importance 

of this technology for everyday life have not really attracted 

any attention from the public at large. However, little is known 

about the technology’s possible health and environmental implications. 

At this critical juncture, it is important that leaders from 

industry, government, the science and engineering community, and 

other sectors develop a better understanding of what the public 

wants and expects of these new and emerging technologies [1-3]. 

The number of projects that encourage the public to engage with 

nanotechnology is growing all the time. However, some scientists 

are uncomfortable with the idea that non-experts should have 

active roles in decisions about nanotechnology, because they are 

often uninformed. Regardless of this opinion, public engagement 

is becoming a serious component of nanotechnology policy in 

many countries [1-6]. Public perception will have a major influence 

on the success of new applications of nanotechnology, as will 

the results of risk assessments carried out by industry on the various 

nanotechnology applications [1, 5-8]. 

Objective 

The aim of this study was to evaluate hospital employee perception 

about nanotechnology in Saudi Arabia and correlate it with 

existing demographic data. 

Methodology 

Three hundred surveys were distributed to employees and trainees 

from different departments in our hospital. The response rate to the 

survey was 40% (120/300). Thirty-nine surveys (33%) were 

excluded because less than 70% of the questionnaire was complet- 

ed. The survey included nine core questions which measured hospital 

workers awareness, perceptions and preferences of nanotechnology. 

Demographic measures, such as age, sex, profession, years 

of experience and level of education, were also recorded. 

Results 

Demographics 

Table 1 shows that we managed to achieve a relatively representative 

distribution of men and women in our sample, with 51% of 

respondents being female. The highest percentage of participants 

(29%) were aged between 30–40 years and the lowest percentage 

(9%) were aged between 50–60 years. At least 68% of respondents 

had achieved a bachelor’s degree and 21% had a doctorate or 

equivalent level. A slight majority of respondents (52%) were 

pharmacists, whilst 21% were physicians. Thirty-five per cent of 

respondents had less than five years’ experience. 

By correlating age with whether workers had heard about nanotechnology, 

we observed a similarity between the group aged 

between 18–25 years and the group aged between 30–40 years. 

Sixteen per cent of each of these two groups reported that they had 

heard of nanotechnology, whilst 11% did not. Six per cent of the 

groups aged 25–30 years and 40–50 years stated that they had not 

heard of nanotechnology, whilst 10% and 14% respectively, had. 

In the 50–60 years age group, 5% had and 5% had not. 

With regards to education, the highest percentage of employees 

who had heard of nanotechnology were those with a doctorate or 

equivalent degree. This was followed by university graduates, university 

undergraduates, and those with a Masters degree (19%, 

15%, 12%, and 9% respectively). 

Table 1: Demographic data (N = 81) 

N = 81 

Age 18–25 25–30 30–40 40–50 50–60 

21 (26%) 13 (16%) 23 (29%) 16 (20%) 7 (9%) 

Sex Male Female N/A 

34 (42%) 41 (51%) 6 

Level of education Doctorate Master University 

graduate 

University 

undergraduate 

Diploma or 

high school 

17 (21%) 10 (13%) 27 (34%) 16 (19%) 11 (13%) 

Profession Medicine Pharmacy Nursing Others 

17 (21%) 42 (52%) 12 (15%) 10 (12%) 

Years of experience < 5 5–10 10–15 15–20 > 20 

28 (35%) 16 (20%) 14 (17%) 7 (8%) 10 (12%) 

N: total number of participants; N/A: not applicable. 


35

Table 2: Questions and answers 

In terms of experience, the highest percentage of employees that 

had heard of nanotechnology was those with less than five years of 

experience. This was followed by those with 10–15 years, those 

with 5–10 years, those with over 20 years, and those with 15–20 

years (17%, 12%, 11%, 7%, and 5% respectively). 

Survey question answers 

Table 2 shows that in general, 61% of people in Saudi Arabia reported 

that they had heard of nanotechnology. The largest proportion of 

respondents (40%) indicated that they heard a little about nanotechnology. 

The majority of the respondents (40%) had heard about nanotechnology 

through the media, while the remaining proportion 

knew about nanotechnology from conferences, Internet, books, and 

other sources respectively. A slim majority of respondents (51%) 

agreed with the statement, ‘Overall, I support the use of nanotechnology 

for human enhancement’. Thirty-eight per cent agreed that 

the benefits of nanotechnology outweighed its risks, 15% agreed that 

its benefits and risks were equal, and 27 % were not sure about the 

risk and benefits of nanotechnology. The majority (47%) indicated 

that they considered that nanotechnology would be very important 

to science and business in the next five years, 21% considered that it 

would be fairly important, and 15% were unsure. Almost 75% indicated 

that they required more information about nanotechnology. 

The majority of respondents also tended to associate nanotechnology 

usage equally within medicine and pharmacy (67% and 65% 

of respondents respectively). 

Conclusion 

Anticipatory governance of emergent technologies depends on a 

comprehensive understanding of the values in society that shape 

public understanding and opinion of new and emerging technolo- 


Have you heard about Yes No 

nanotechnology? 50 (61%) 31 (39%) 

How much have you A lot Some A little Nothing Not sure 

heard, read or seen about 5 (7%) 18 (22%) 32 (40%) 11 (14%) 3 (4%) 

using nanotechnology? 

How did you know about Conference Media Internet Books Others 

nanotechnology? 20 (25%) 32 (40%) 21 (26%) 5 (6%) 6 (7%) 

I support use of nano- Agree Slightly agree Do not know Slightly disagree Disagree 

technology for human 41 (51%) 9 (11%) 16 (20%) Not applicable 1 (2%) 

enhancement 

What is your initial Benefits Benefits and risks Risks outweigh Not sure 

impression of risks and outweigh risks are equal benefits 

benefits of nanotechnology? 31 (38%) 12 (15%) Not applicable 22 (27%) 

Rate the impression of Very important Fairly important Not too Not at all Do not know 

nanotechnology to science important important 

and business in the next 38 (47%) 17 (21%) Not applicable Not applicable 12 (15%) 

five years 

Do you feel that you need Yes No Not interested 

to know more information 61 (75%) Not applicable 5 (6%) 

about nanotechnology? 

Do you recommend to Yes No Do not know 

policy makers to provide 49 (61%) Not applicable 16 (20%) 

more information to 

hospital workers about 

nanotechnology? 

gies, and of related current technologies. This survey aimed to 

measure and evaluate the understanding of public values about nanotechnology 

in Saudi Arabia, as presented by hospital workers. 

Public opinion research should be considered a vital element in any 

attempt to assess a developing technology, and in any subsequent 

efforts at anticipatory governance. Further research is highly recommended. 

In addition, we recommend that policy makers should 

increase hospital employee awareness about nanotechnology 

through continuous scientific events. This may lead to improved 

understanding and indirect future advances in nanotechnology. We 

plan to re-evaluate and assess the workers’perceptions in five years 

time. A comparison of available data with the international public 

perception about nanotechnology is also recommended. 

Authors 

Nagwa Ibrahim, PharmD, FAIHQ 

Clinical Pharmacist Specialist 


Ali Al Zahrani, MD, FRCR 

Director, Consultant 

Oncology Department 

Ashraf Al Alwan, PhD 

Assistant Director, Consultant Clinical Pharmacist 

Clinical Services, Pharmacy Department 

Riyadh Military Hospital 

PO Box 7897 

SA-11159 Riyadh, Saudi Arabia 

References

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